Athletes seeking to avoid testing positive use various methods. The most common methods include:

- Urine replacement, which involves replacing dirty urine with clean urine from someone who is not taking banned substances. Urine replacement can be done by catheterization or with a prosthetic penis such as The Original Whizzinator.

- Diuretics, used to cleanse the system before having to provide a sample.

- Blood transfusions, which increase the blood's oxygen carrying capacity, in turn increasing endurance without the presence of drugs that could trigger a positive test result.

Cheating at the Paralympic Games has caused scandals that have significantly changed the way in which the International Paralympic Committee (IPC) manages the events.

Testing for performance-enhancing drugs has become increasingly strict and more widespread throughout the Games, with powerlifting seeing the most positive results. Competitors without disabilities have also competed in some Paralympic Games, with the Spanish entry in the intellectually disabled basketball tournament at the 2000 Summer Paralympics being the most controversial.

Side effects in women include:

- hair loss

- male pattern baldness

- hypertrophy of the clitoris

- increased sex drive

- irregularities of the menstrual cycle

- development of masculine facial traits

- increased coarseness of the skin

- premature closure of the epiphysis

In countries where the use of these drugs is controlled, there is often a black market trade of smuggled or counterfeit drugs. The quality of these drugs may be poor and can cause health risks. In countries where anabolic steroids are strictly regulated, some have called for a regulatory relief. Steroids are available over-the-counter in some countries such as Thailand and Mexico.

The Lance Armstrong doping case was a doping investigation that led to American former professional road racing cyclist Lance Armstrong being stripped of his seven Tour de France titles and his eventual admission to the doping.

The 2007 Tour de France was affected by a series of scandals and speculations related to doping. By the end of the Tour, two cyclists were dismissed for failing tests and the wearer of the yellow jersey was voluntarily retired by his team for lying about his whereabouts and missing doping tests. A fourth rider was confirmed to having used doping while in a training session prior to the 2007 Tour and a fifth rider failed tests late in the race, with his result being officially announced just after the end of the Tour. During the competition, two teams were asked to withdraw after at least one member was found to have doped.

The events generated criticism and a general distrustful attitude toward the sport of professional cycling from media and public opinion. The doping allegations also resulted in several team sponsors threatening to retire their support if events advanced further. Some media such as German TV channels ARD and ZDF left the Tour once the first scandals broke. Following the Tour's conclusion, the sport's governing bodies spoke out about ways to combat the prevalence of doping in cycling and key team sponsors elected to withdraw their support due to the reputational damage caused by the scandals. The 2007 Tour de France has been referred to as one of the most controversial Tours. After the end of the Tour, "The Times" of London ranked it 4th in its list of the top 50 sporting scandals.

Doping in Russian sports has a systemic nature. Russia has had 51 Olympic medals stripped for doping violations – the most of any country, four times the number of the runner-up, and more than a third of the global total. From 2011 to 2015, more than a thousand Russian competitors in various sports, including summer, winter, and Paralympic sports, benefited from a cover-up.

States that agree to the Convention align their domestic rules with the World Anti-Doping Code, which is promulgated by the World Anti-Doping Agency. This includes facilitating doping controls and supporting national testing programmes; encouraging the establishment of "best practice" in the labelling, marketing, and distribution of products that might contain prohibited substances; withholding financial support from those who engage in or support doping; taking measures against manufacturing and trafficking; encouraging the establishment of codes of conduct for professions relating to sport and anti-doping; and funding education and research on drugs in sport.

For much of the second phase of his career, Cyclist Lance Armstrong faced constant allegations of doping. Armstrong consistently denied allegations of doping until a partial confession during a broadcast interview with Oprah Winfrey in January 2013.

The World Anti-Doping Agency (WADA) is the main regulatory organization looking into the issue of the detection of gene doping. Both direct and indirect testing methods are being researched by the organization. Directly detecting the use of gene therapy usually requires the discovery of recombinant proteins or gene insertion vectors, while most indirect methods involve examining the athlete in an attempt to detect bodily changes or structural differences between endogenous and recombinant proteins.

Indirect methods are by nature more subjective, as it becomes very difficult to determine which anomalies are proof of gene doping, and which are simply natural, though unusual, biological properties. For example, Eero Mäntyranta, an Olympic cross country skier, had a mutation which made his body produce abnormally high amounts of red blood cells. It would be very difficult to determine whether or not Mäntyranta's red blood cell levels were due to an innate genetic advantage, or an artificial one.

There have been allegations of doping in the Tour de France since the race began in 1903. Early Tour riders consumed alcohol and used ether, among other substances, as a means of dulling the pain of competing in endurance cycling. Riders began using substances as a means of increasing performance rather than dulling the senses, and organizing bodies such as the "Tour" and the International Cycling Union (UCI), as well as government bodies, enacted policies to combat the practice.

Use of performance-enhancing drugs in cycling predates the Tour de France. Cycling, having been from the start a sport of extremes, whether of speed by being paced by tandems, motorcycles and even cars, or of distance, the suffering involved encouraged the means to alleviate it. Not until after World War II were sporting or even particularly health issues raised. Those came shortly before the death of Tom Simpson in the Tour de France of 1967. Max Novich referred to the Tour de France in a 1973 issue of "New York State Journal of Medicine" as "a cycling nightmare". In the eyes of a 1998 German observer:

The International Convention against Doping in Sport is a multilateral UNESCO treaty by which states agree to adopt national measures to prevent and eliminate drug doping in sport.

The World Anti-Doping Agency (WADA) determined that non therapeutic form of genetic manipulation for enhancement of athletic performance is not allowed in sport. The WADA code implemented guidelines to determine if said technology should be prohibited in sport. If two of the three conditions are met, then the technology is prohibited in sport; harmful to one's health, performance enhancing, and/or against the "spirit of sport". The high risks associated with gene therapy can be outweighed by the potential save the lives of individuals with diseases. According to Alain Fischer, who was involved in clinical trials of gene therapy in children with severe combined immunodeficiency, "Only people who are dying would have reasonable grounds for using it. Using gene therapy for doping is ethically unacceptable and scientifically stupid." As seen with past cases, including the steroid tetrahydrogestrinone THG, athletes may choose to incorporate risky genetic technologies into their training regimes.

The mainstream perspective is that gene doping is dangerous and unethical, as is any application of a therapeutic intervention for non-therapeutic or enhancing purposes, and that it compromises the ethical foundation of medicine and the spirit of sport. Others, who support human enhancement on broader grounds, or who see a false dichotomy between "natural" and "artificial" or a denial of the role of technology in improving athletic performance, do not oppose or support gene doping.

14 of the 25 most recent winners (56%) have either failed tests or have confessed to have used doping. Together with those who failed tests but never sanctioned, 68% of the winners evidently used doping as detailed in the table below.

Since the introduction of doping tests in 1964, many cyclists were caught in the Tour de France. In recent years, 1996 Tour de France winner Bjarne Riis and points classification winner Erik Zabel, along with most of their Team Telekom team-mates, confessed to using erythropoietin (EPO). In 1997, former points classification winner Djamolidine Abdoujaparov was disqualified from the Tour de France for doping use. In 1998, the Festina affair had several main contenders removed from the race. In the next years, several riders were removed from the Tour de France for doping (see List of doping cases in cycling).

In addition, several riders were not allowed to start the previous Tour, including Jan Ullrich and Ivan Basso because of their involvement in the Operación Puerto doping case, a Spanish investigation against doctor Eufemiano Fuentes and a number of accomplices accused of administering prohibited doping products to approximately two hundred professional athletes, to enhance their performance.

After the completion of the 2006 Tour, winner Floyd Landis was found to have an elevated testosterone to epitestosterone ratio on a sample taken following Stage 17 of the race, and at the time of the 2007 Tour prologue. Since the results of an independent arbitration hearing were still pending Landis was prevented from defending his title. He was stripped of his 2006 Tour title in September 2007.

Abortion doping refers to the rumoured practice of purposely inducing pregnancy for athletic performance-enhancing benefits, then aborting the pregnancy.

Travelling west causes fewer problems than travelling east, and it is usually sufficient to seek exposure to light during the day and avoid it at night.

Travelling east causes more problems than travelling west because the body clock has to be advanced, which is more difficult for the majority of humans than delaying it. Most people have an endogenous circadian rhythm that is longer than 24 hours, so lengthening a day is less troublesome than shortening it. Equally important, the necessary exposure to light to realign the body clock does not tie in with the day/night cycle at the destination.

Travelling east by six to nine time zones causes the biggest problems, as it is desirable to avoid light in the mornings. Waterhouse et al. recommend:

Travelling by 10 hours or more is usually best managed by assuming it is a 14-hour westward transition and delaying the body clock. A customised jet lag program can be obtained from an online jet lag calculator. These programs consider the sleep pattern of the user, the number of time zones crossed, and the direction of travel. The efficacy of these jet lag calculators has not been documented.

Hormonal and other changes in pregnancy affect physical performance. In the first three months it is known that a woman’s body produces a natural surplus of red blood cells, which are well supplied with oxygen-carrying hemoglobin, in order to support the growing fetus. A study of athletes before and after pregnancy by Professor James Pivarnik at the Human Energy Research laboratory in Michigan State University has found there is a 60 per cent increase in blood volume and that this could improve the body’s ability to carry oxygen to muscles by up to 30 percent. This would have obvious positive effects on aerobic capacity. Other potential advantages are obtained from the surge in hormones that pregnancy induces, predominantly progesterone and estrogen, but also testosterone, which could increase muscle strength. Increases in hormones like relaxin, which loosens the hip joints to prepare for childbirth, may have a performance-enhancing effect on joint mobility.

Several world records have been set by female athletes shortly after giving birth to their first child. This is accepted as a natural and unintended event.

The IPC announced that, due to serious difficulties in determining the eligibility of athletes, it was suspending all official sporting activities involving an intellectual disability. The IPC attempted to develop a revised system for testing for intellectual disabilities but announced on 1 February 2003 that all events involving learning difficulties would be abandoned for the 2004 Summer Paralympics in Athens.

Following an anti-corruption drive, the International Sports Federation for Persons with an Intellectual Disability (INAS-FID) lobbied to have these athletes reinstated. Beginning in 2004, athletes with an intellectual disability began to be re-integrated into Paralympic sport competitions. The IPC stated that it would re-evaluate their participation following the Beijing 2008 Paralympic Games. In November 2009 the ban was lifted and the IPC introduced a series of "sports intelligence" tests to confirm claimed disabilities. The first IPC-run event where intellectual disability athletes were allowed to compete again was the 2009 IPC Swimming European Championships.

According to British journalist Andrew Jennings, a KGB colonel stated that the agency's officers had posed as anti-doping authorities from the International Olympic Committee to undermine doping tests and that Soviet athletes were "rescued with [these] tremendous efforts". On the topic of the 1980 Summer Olympics, a 1989 Australian study said "There is hardly a medal winner at the Moscow Games, certainly not a gold medal winner, who is not on one sort of drug or another: usually several kinds. The Moscow Games might as well have been called the Chemists' Games."

Documents obtained in 2016 revealed the Soviet Union's plans for a statewide doping system in track and field in preparation for the 1984 Summer Olympics in Los Angeles. Dated prior to the country's decision to boycott the Games, the document detailed the existing steroids operations of the program, along with suggestions for further enhancements. The communication, directed to the Soviet Union's head of track and field, was prepared by Dr. Sergei Portugalov of the Institute for Physical Culture. Portugalov was also one of the main figures involved in the implementation of the Russian doping program prior to the 2016 Summer Olympics.

For much of his career, Lance Armstrong faced persistent allegations of doping, but until 2006 no official investigation was undertaken. The first break in the case came in 2004, when SCA Promotions, a Dallas-based insurer, balked at paying a $5 million bonus to Armstrong for winning his sixth consecutive Tour. SCA president Bob Hamman had read "L.A. Confidentiel", a book by cycling journalists Pierre Ballester and David Walsh which detailed circumstantial evidence of massive doping by Armstrong and members of his U.S. Postal Service Pro Cycling Team. In 2006, an arbitration panel ruled that SCA had to pay. However, Hamman's real goal was to force an investigation by sporting authorities. He believed that if someone in a position to investigate the matter found that Armstrong had indeed doped, he could be stripped of his Tour victories--allowing SCA to get its money back. His hunch proved correct; officials from the United States Anti-Doping Agency (USADA) asked to review the evidence Hamman had gleaned.

Armstrong has been criticized for his disagreements with outspoken opponents of doping such as Paul Kimmage and Christophe Bassons. Bassons wrote a number of articles for a French newspaper during the 1999 Tour de France which made references to doping in the peloton. Subsequently, Armstrong had an altercation with Bassons during the 1999 Tour de France where Bassons said Armstrong rode up alongside on the Alpe d'Huez stage to tell him "it was a mistake to speak out the way I (Bassons) do and he (Armstrong) asked why I was doing it. I told him that I'm thinking of the next generation of riders. Then he said 'Why don't you leave, then?'"

Armstrong later confirmed Bassons's story. On the main evening news on TF1, a French television station, Armstrong said: "His accusations aren't good for cycling, for his team, for me, for anybody. If he thinks cycling works like that, he's wrong and he would be better off going home". Kimmage, a professional cyclist in the 1980s who later became a sports journalist, referred to Armstrong as a "cancer in cycling". He also asked Armstrong questions in relation to his "admiration for dopers" at a press conference at the Tour of California in 2009, provoking a scathing reaction from Armstrong. This spat continued and is exemplified by Kimmage's articles in "The Sunday Times".

Another notable critic of Armstrong was David Walsh, also a reporter for "The Sunday Times". Referred to as a "little troll" by Armstrong, Walsh revealed in a 2001 "Sunday Times" story that he had ties to controversial Italian doctor Michele Ferrari. Two years later, Walsh's book "L.A. Confidentiel" alleged, based on testimony by Armstrong's former masseuse Emma O'Reilly, that clandestine trips were made to pick up and deliver doping products to Armstrong's team.

Until his 2013 admission, Armstrong continually denied using illegal performance-enhancing drugs and described himself as the most tested athlete in the world. However, a 1999 urine sample showed traces of corticosteroid; a medical certificate showed he used an approved cream for saddle sores which contained the substance. O'Reilly claimed that team officials conspired with a compliant doctor to falsify Armstrong's prescription, and that Armstrong never had the condition. She also claimed that, on other occasions, she was asked to dispose of used syringes for Armstrong and pick up strange parcels for the team.

From his return to cycling in the fall of 2008 through March 2009, Armstrong submitted to twenty-four unannounced drug tests by various anti-doping authorities. All of the tests were negative for performance-enhancing drugs.

U.S. federal prosecutors pursued allegations of doping by Armstrong from 2010–2012. The effort convened a grand jury to investigate doping charges, including taking statements under oath from Armstrong's former team members and other associates; met with officials from France, Belgium, Spain, and Italy; and requested samples from the French anti-doping agency. The investigation was led by federal agent Jeff Novitzky, who also investigated suspicions of steroid use by baseball players Barry Bonds and Roger Clemens. The probe was terminated on February 3, 2012 with no charges filed.

Tyler Hamilton, a professional cyclist who rode as Lance Armstrong's principal Domestique on the U.S. Postal Cycling team from 1999 through 2001, has extensively documented the history and methods of doping by Armstrong, himself, and others in "The Secret Race", a book co-authored with Daniel Coyle and published in 2012. The book also describes the investigation by Jeff Novitzky and the Food and Drug Administration and Hamilton's befuddlement that the investigation was dropped.

Relative polycythemia is an apparent rise of the erythrocyte level in the blood; however, the underlying cause is reduced blood plasma (hypovolemia, cf. dehydration). Relative polycythemia is often caused by loss of body fluids, such as through burns, dehydration, and stress. A specific type of relative polycythemia is Gaisböck syndrome. In this syndrome, primarily occurring in obese men, hypertension causes a reduction in plasma volume, resulting in (amongst other changes) a relative increase in red blood cell count.

Secondary polycythemia is caused by either natural or artificial increases in the production of erythropoietin, hence an increased production of erythrocytes. In secondary polycythemia, 6 to 8 million and occasionally 9 million erythrocytes may occur per millimeter of blood. Secondary polycythemia resolves when the underlying cause is treated.

Secondary polycythemia in which the production of erythropoietin increases appropriately is called physiologic polycythemia.

Conditions which may result in a physiologically appropriate polycythemia include:

- Altitude related - This physiologic polycythemia is a normal adaptation to living at high altitudes (see altitude sickness). Many athletes train at high altitude to take advantage of this effect — a legal form of blood doping. Some individuals believe athletes with primary polycythemia may have a competitive advantage due to greater stamina. However, this has yet to be proven due to the multifaceted complications associated with this condition.

- Hypoxic disease-associated - for example in cyanotic heart disease where blood oxygen levels are reduced significantly, may also occur as a result of hypoxic lung disease such as COPD and as a result of chronic obstructive sleep apnea.

- Iatrogenic - Secondary polycythemia can be induced directly by phlebotomy (blood letting) to withdraw some blood, concentrate the erythrocytes, and return them to the body.

- Genetic - Heritable causes of secondary polycythemia also exist and are associated with abnormalities in hemoglobin oxygen release. This includes patients who have a special form of hemoglobin known as Hb Chesapeake, which has a greater inherent affinity for oxygen than normal adult hemoglobin. This reduces oxygen delivery to the kidneys, causing increased erythropoietin production and a resultant polycythemia. Hemoglobin Kempsey also produces a similar clinical picture. These conditions are relatively uncommon.

Conditions where the secondary polycythemia is not as a result of physiologic adaptation and occurs irrespective of body needs include:

- Neoplasms - Renal-cell carcinoma or liver tumors, von Hippel-Lindau disease, and endocrine abnormalities including pheochromocytoma and adrenal adenoma with Cushing's syndrome.

- People whose testosterone levels are high because of the use of anabolic steroids, including athletes who abuse steroids, or people on testosterone replacement for hypogonadism or transgender hormone replacement therapy, as well as people who take erythropoietin, may develop secondary polycythemia.