It is hard to differentiate a viral and a bacterial cause of a sore throat based on symptoms alone. Thus often a throat swab is done to rule out a bacterial cause.

The modified Centor criteria may be used to determine the management of people with pharyngitis. Based on 5 clinical criteria, it indicates the probability of a streptococcal infection.

One point is given for each of the criteria:

- Absence of a cough

- Swollen and tender cervical lymph nodes

- Temperature >

- Tonsillar exudate or swelling

- Age less than 15 (a point is subtracted if age >44)

The McIsaac criteria adds to the Centor:

- Age less than 15: add one point

- Age greater than 45: subtract one point

The Infectious Disease Society of America however recommends against empirical treatment and considers antibiotics only appropriate following positive testing. Testing is not needed in children under three as both group A strep and rheumatic fever are rare, except if they have a sibling with the disease.

The diagnosis of group A beta-hemolytic streptococcus (GABHS) tonsillitis can be confirmed by culture of samples obtained by swabbing both tonsillar surfaces and the posterior pharyngeal wall and plating them on sheep blood agar medium. The isolation rate can be increased by incubating the cultures under anaerobic conditions and using selective growth media. A single throat culture has a sensitivity of 90–95% for the detection of GABHS (which means that GABHS is actually present 5–10% of the time culture suggests that it is absent). This small percentage of false-negative results are part of the characteristics of the tests used but are also possible if the patient has received antibiotics prior to testing. Identification requires 24 to 48 hours by culture but rapid screening tests (10–60 minutes), which have a sensitivity of 85–90%, are available. Older antigen tests detect the surface Lancefield group A carbohydrate. Newer tests identify GABHS serotypes using nucleic acid (DNA) probes or polymerase chain reaction. Bacterial culture may need to be performed in cases of a negative rapid streptococcal test.

True infection with GABHS, rather than colonization, is defined arbitrarily as the presence of >10 colonies of GABHS per blood agar plate. However, this method is difficult to implement because of the overlap between carriers and infected patients. An increase in antistreptolysin O (ASO) streptococcal antibody titer 3–6 weeks following the acute infection can provide retrospective evidence of GABHS infection and is considered definitive proof of GABHS infection.

Increased values of secreted phospholipase A2 and altered fatty acid metabolism in patients with tonsillitis may have diagnostic utility.

A throat culture is the gold standard for the diagnosis of streptococcal pharyngitis, with a sensitivity of 90–95%. A rapid strep test (also called rapid antigen detection testing or RADT) may also be used. While the rapid strep test is quicker, it has a lower sensitivity (70%) and statistically equal specificity (98%) as a throat culture. In areas of the world where rheumatic fever is uncommon, a negative rapid strep test is sufficient to rule out the disease.

A positive throat culture or RADT in association with symptoms establishes a positive diagnosis in those in which the diagnosis is in doubt. In adults, a negative RADT is sufficient to rule out the diagnosis. However, in children a throat culture is recommended to confirm the result. Asymptomatic individuals should not be routinely tested with a throat culture or RADT because a certain percentage of the population persistently "carries" the streptococcal bacteria in their throat without any harmful results.

As the symptoms of streptococcal pharyngitis overlap with other conditions, it can be difficult to make the diagnosis clinically. Coughing, nasal discharge, diarrhea, and red, irritated eyes in addition to fever and sore throat are more indicative of a viral sore throat than of strep throat. The presence of marked lymph node enlargement along with sore throat, fever, and tonsillar enlargement may also occur in infectious mononucleosis.

Acute pharyngitis is the most common cause of a sore throat and, together with cough, it is diagnosed in more than 1.9 million people a year in the United States.

Treatments to reduce the discomfort from tonsillitis include:

- pain and fever reducing medications such as paracetamol (acetaminophen) and ibuprofen

- warm salt water gargle, lozenges, or warm liquids

When tonsillitis is caused by a virus, the length of illness depends on which virus is involved. Usually, a complete recovery is made within one week; however, symptoms may last for up to two weeks.

The diagnosis of a throat irritation include a physical exam and throat culture.

There is low or very-low quality evidence that probiotics may be better than placebo in preventing acute URTIs. Vaccination against influenza viruses, adenoviruses, measles, rubella, "Streptococcus pneumoniae", "Haemophilus influenzae", diphtheria, "Bacillus anthracis", and "Bordetella pertussis" may prevent them from infecting the URT or reduce the severity of the infection.

Diagnosis is by a swab of the affected area for laboratory testing. A Gram stain is performed to show Gram-positive cocci in chains. Then, the organism is cultured on blood agar with an added bacitracin antibiotic disk to show beta-hemolytic colonies and sensitivity (zone of inhibition around the disk) for the antibiotic. Culture on agar not containing blood, and then performing the catalase test should show a negative reaction for all streptococci. "S. pyogenes" is CAMP and hippurate tests negative. Serological identification of the organism involves testing for the presence of group-A-specific polysaccharide in the bacterium's cell wall using the Phadebact test.

The rapid pyrrolidonyl arylamidase (PYR) test is used for the presumptive identification of group A beta-hemolytic streptococci. GBS gives a negative finding on this test.

The Centers for Disease Control describe protocol for treating sinusitis while at the same time discouraging overuse of antibiotics:

- Target likely organisms with first-line drugs: Amoxicillin, Amoxicillin/Clavulanate

- Use shortest effective course: Should see improvement in 2–3 days. Continue treatment for 7 days after symptoms improve or resolve (usually a 10–14 day course).

- Consider imaging studies in recurrent or unclear cases: some sinus involvement is frequent early in the course of uncomplicated viral URI

Treatment comprises symptomatic support usually via analgesics for headache, sore throat and muscle aches. Moderate exercise in sedentary subjects with naturally acquired URTI probably does not alter the overall severity and duration of the illness. No randomized trials have been conducted to ascertain benefits of increasing fluid intake.

The distinction between viral upper respiratory tract infections is loosely based on the location of symptoms with the common cold affecting primarily the nose, pharyngitis the throat, and bronchitis the lungs. However, there can be significant overlap and multiple areas can be affected. The common cold is frequently defined as nasal inflammation with varying amount of throat inflammation. Self-diagnosis is frequent. Isolation of the viral agent involved is rarely performed, and it is generally not possible to identify the virus type through symptoms.

The majority of cases of throat irritation usually go away without any treatment. There is no real treatment for throat irritation from a virus. If you have difficulty swallowing then one should drink liquids, suck on lozenges, ice chips or mix salt with warm water to gargle. Bacterial infections generally require antibiotics.

Home remedies for throat irritation include gargling with warm water twice a day, sipping honey and lemon mixture or sucking on medicated lozenges. If the cause is dry air, then one should humidify the home. Since smoke irritates the throat, stop smoking and avoid all fumes from chemicals, paints and volatile liquids.

Rest your voice if you have been screaming or singing. If you have pharyngitis, avoid infecting others by covering your mouth when coughing and wear a mask.

Diagnosis is usually based on the symptoms. Medical imaging may be done to rule out complications. Medical imaging may include CT scan or MRI.

The pus can be removed by a number of methods including needle aspiration, incision and drainage, and tonsillectomy.

Treatment can also be given while a patient is under anesthesia, but this is usually reserved for children or anxious patients. Tonsillectomy can be indicated if a patient has recurring peritonsillar abscesses or a history of tonsillitis. For patients with their first peritonsillar abscess most ENT-surgeons prefer to "wait and observe" before recommending tonsillectomy.

The only useful ways to reduce the spread of cold viruses are physical measures such as hand washing and face masks; in the healthcare environment, gowns and disposable gloves are also used. Isolation or quarantine is not used as the disease is so widespread and symptoms are non-specific. Vaccination has proved difficult as there are many viruses involved and they mutate rapidly. Creation of a broadly effective vaccine is, thus, highly improbable.

Regular hand washing appears to be effective in reducing the transmission of cold viruses, especially among children. Whether the addition of antivirals or antibacterials to normal hand washing provides greater benefit is unknown. Wearing face masks when around people who are infected may be beneficial; however, there is insufficient evidence for maintaining a greater social distance.

It is unclear if zinc supplements affect the frequency of colds. Routine vitamin C supplements do not reduce the risk or severity of the common cold, though they may reduce its duration. Gargling with water was found useful in one small trial.

"S. pyogenes" infections are best prevented through effective hand hygiene. No vaccines are currently available to protect against "S. pyogenes" infection, although research has been conducted into the development of one. Difficulties in developing a vaccine include the wide variety of strains of "S. pyogenes" present in the environment and the large amount of time and number of people that will be needed for appropriate trials for safety and efficacy of the vaccine.

Antigen detection, polymerase chain reaction assay, virus isolation, and serology can be used to identify adenovirus infections. Adenovirus typing is usually accomplished by hemagglutination-inhibition and/or neutralization with type-specific antisera. Since adenovirus can be excreted for prolonged periods, the presence of virus does not necessarily mean it is associated with disease.

The heterophile antibody test works by agglutination of red blood cells from guinea pig, sheep and horse. This test is specific but not particularly sensitive (with a false-negative rate of as high as 25% in the first week, 5–10% in the second, and 5% in the third). About 90% of patients have heterophile antibodies by week 3, disappearing in under a year. The antibodies involved in the test do not interact with the Epstein–Barr virus or any of its antigens.

The monospot test is not recommended for general use by the CDC due to its poor accuracy.

A 2014 systematic review of clinical trials does not support using routine rapid viral testing to decrease antibiotic use for children in emergency departments. It is unclear if rapid viral testing in the emergency department for children with acute febrile respiratory infections reduces the rates of antibiotic use, blood testing, or urine testing. The relative risk reduction of chest x-ray utilization in children screened with rapid viral testing is 77% compared with controls. In 2013 researchers developed a breath tester that can promptly diagnose lung infections.

About 10% of people who present a clinical picture of infectious mononucleosis do not have an acute Epstein–Barr-virus infection. A differential diagnosis of acute infectious mononucleosis needs to take into consideration acute cytomegalovirus infection and "Toxoplasma gondii" infections. Because their management is much the same, it is not always helpful, or possible, to distinguish between Epstein–Barr-virus mononucleosis and cytomegalovirus infection. However, in pregnant women, differentiation of mononucleosis from toxoplasmosis is important, since it is associated with significant consequences for the fetus.

Acute HIV infection can mimic signs similar to those of infectious mononucleosis, and tests should be performed for pregnant women for the same reason as toxoplasmosis.

People with infectious mononucleosis are sometimes misdiagnosed with a streptococcal pharyngitis (because of the symptoms of fever, pharyngitis and adenopathy) and are given antibiotics such as ampicillin or amoxicillin as treatment.

Other conditions from which to distinguish infectious mononucleosis include leukemia, tonsillitis, diphtheria, common cold and influenza (flu).

Safe and effective adenovirus vaccines were developed for adenovirus serotypes 4 and 7, but were available only for preventing ARD among US military recruits, and production stopped in 1996. Strict attention to good infection-control practices is effective for stopping transmission in hospitals of adenovirus-associated disease, such as epidemic keratoconjunctivitis. Maintaining adequate levels of chlorination is necessary for preventing swimming pool-associated outbreaks of adenovirus conjunctivitis.

Normal surgical masks and N95 masks appear equivalent with respect to preventing respiratory infections.

"M. pneumoniae" infections can be differentiated from other types of pneumonia by the relatively slow progression of symptoms. A positive blood test for cold-hemagglutinins in 50–70% of patients after 10 days of infection (cold-hemagglutinin-test should be used with caution or not at all, since 50% of the tests are false-positive), lack of bacteria in a Gram-stained sputum sample, and a lack of growth on blood agar.

PCR has also been used.

According to present research, PFAPA does not lead to other diseases and spontaneously resolves as the child gets older, with no long term physical effects.

However, PFAPA has been found in adults and may not spontaneously resolve.

Although the presentation of scarlet fever can be clinically diagnosed, further testing may be required to distinguish it from other illnesses. Also, history of a recent exposure to someone with strep throat can be useful. There are two methods used to confirm suspicion of scarlet fever rapid antigen detection test and throat culture.

The rapid antigen detection test is a very specific test but not very sensitive. This means that if the result is positive (indicating that the Group A Strep Antigen was detected and therefore confirming that the patient has a Group A Strep Pharyngitis) then it is appropriate to treat them with antibiotics. However, if the Rapid Antigen Detection Test is negative (indicating that they do not have Group A Strep Pharyngitis), then a throat culture is required to confirm since it could be a false negative result. The throat culture is the current gold standard for diagnosis.

Serologic testing looks for the antibodies that the body produces against the streptococcal infection including antistreptolysin-O and antideoxyribonuclease B. It takes the body 2–3 weeks to make these antibodies so this type of testing is not useful for diagnosing a current infection. However, it is useful when assessing a patient who may have one of the complications from a previous streptococcal infection.

Throat cultures done after antibiotic therapy can tell you if the infection has been removed. These throat swabs however are not indicated because up to 25% of properly treated individuals can continue to carry the streptococcal infection while asymptomatic.