The mainstay of treatment is antibiotics. Phenazopyridine is occasionally prescribed during the first few days in addition to antibiotics to help with the burning and urgency sometimes felt during a bladder infection. However, it is not routinely recommended due to safety concerns with its use, specifically an elevated risk of methemoglobinemia (higher than normal level of methemoglobin in the blood). Acetaminophen (paracetamol) may be used for fevers. There is no good evidence for the use of cranberry products for treating current infections.

Uncomplicated infections can be diagnosed and treated based on symptoms alone. Antibiotics taken by mouth such as trimethoprim/sulfamethoxazole (TMP/SMX), nitrofurantoin, or fosfomycin are typically first line. Cephalosporins, amoxicillin/clavulanic acid, or a fluoroquinolone may also be used. However, resistance to fluoroquinolones among the bacterial that cause urinary infections has been increasing. The FDA recommends against the use of fluoroquinolones when other options are available due to higher risks of serious side effects. These medications substantially shorten the time to recovery with all being equally effective. A three-day treatment with trimethoprim, TMP/SMX, or a fluoroquinolone is usually sufficient, whereas nitrofurantoin requires 5–7 days. Fosfomycin may be used as a single dose but has been associated with lower rates of efficacy.

With treatment, symptoms should improve within 36 hours. About 50% of people will recover without treatment within a few days or weeks. Fluoroquinolones are not recommended as a first treatment. The Infectious Diseases Society of America states this due to the concern of generating resistance to this class of medication. Amoxicillin-clavulanate appears less effective than other options. Despite this precaution, some resistance has developed to all of these medications related to their widespread use. Trimethoprim alone is deemed to be equivalent to TMP/SMX in some countries. For simple UTIs, children often respond to a three-day course of antibiotics. Women with recurrent simple UTIs may benefit from self-treatment upon occurrence of symptoms with medical follow-up only if the initial treatment fails.

Over time, the relapse rate is high, exceeding 50%. However, recent research indicates that combination therapies offer a better prognosis than antibiotics alone.

A 2007 study showed that repeated combination pharmacological therapy with antibacterial agents (ciprofloxacin/azithromycin), alpha-blockers (alfuzosin) and Serenoa repens extracts may eradicate infection in 83.9% of patients with clinical remission extending throughout a follow-up period of 30 months for 94% of these patients.

A 2014 study of 210 patients randomized into two treatment groups found that recurrence occurred within 2 months in 27.6% of the group using antibiotics alone (prulifloxacin 600 mg), but in only 7.8% of the group taking prulifloxacin in combination with Serenoa repens extract, Lactobacillus Sporogens and Arbutin.

People with acute pyelonephritis that is accompanied by high fever and leukocytosis are typically admitted to the hospital for intravenous hydration and intravenous antibiotic treatment. Treatment is typically initiated with an intravenous fluoroquinolone, an aminoglycoside, an extended-spectrum penicillin or cephalosporin, or a carbapenem. Combination antibiotic therapy is often used in such situations. The treatment regimen is selected based on local resistance data and the susceptibility profile of the specific infecting organism(s).

During the course of antibiotic treatment, serial white blood cell count and temperature are closely monitored. Typically, the intravenous antibiotics are continued until the person has no fever for at least 24 to 48 hours, then equivalent antibiotics by mouth can be given for a total of 2–week duration of treatment. Intravenous fluids may be administered to compensate for the reduced oral intake, insensible losses (due to the raised temperature) and vasodilation and to optimize urine output. Percutaneous nephrostomy or ureteral stent placement may be indicated to relieve obstruction caused by a stone. Children with acute pyelonephritis can be treated effectively with oral antibiotics (cefixime, ceftibuten and amoxicillin/clavulanic acid) or with short courses (2 to 4 days) of intravenous therapy followed by oral therapy. If intravenous therapy is chosen, single daily dosing with aminoglycosides is safe and effective.

Treatment of xanthogranulomatous pyelonephritis involves antibiotics as well as surgery. Removal of the kidney is the best surgical treatment in the overwhelming majority of cases, although polar resection (partial nephrectomy) has been effective for some people with localized disease. Watchful waiting with serial imaging may be appropriate in rare circumstances.

Symptomatic bacteriuria is typically treated as a urinary tract infection with antibiotics. Common choices include nitrofurantoin, and trimethoprim/sulfamethoxazole.

Asymptomatic bacteriuria generally does not require treatment. Exceptions include during pregnancy and in those undergoing surgery of the urinary tract. Children with vesicoureteral reflux or others with structural abnormalities of the urinary tract.

There is no indication to treat asymptomatic bacteriuria in diabetics, renal transplant recipients, and in those with spinal cord injuries.

The overuse of antibiotic therapy to treat asymptomatic bacteriuria increases the risk of diarrhea, antimicrobial resistance, and infection due to Clostridium difficile. Other effects include increased financial burdens and overreporting of mandated catheter-associated urinary tract infection.

In people who do not require hospitalization and live in an area where there is a low prevalence of antibiotic-resistant bacteria, an fluoroquinolone by mouth such as ciprofloxacin or levofloxacin is an appropriate initial choice for therapy. In areas where there is a higher prevalence of fluoroquinolone resistance, it is useful to initiate treatment with a single intravenous dose of a long-acting antibiotic such as ceftriaxone or an aminoglycoside, and then continuing treatment with a fluoroquinolone. Oral trimethoprim/sulfamethoxazole is an appropriate choice for therapy if the bacteria is known to be susceptible. If trimethoprim/sulfamethoxazole is used when the susceptibility is not known, it is useful to initiate treatment with a single intravenous dose of a long-acting antibiotic such as ceftriaxone or an aminoglycoside. Oral beta-lactam antibiotics are less effective than other available agents for treatment of pyelonephritis. Improvement is expected in 48 to 72 hours.

Antibiotic therapy has to overcome the blood/prostate barrier that prevents many antibiotics from reaching levels that are higher than minimum inhibitory concentration. A blood-prostate barrier restricts cell and molecular movement across the rat ventral prostate epithelium. Treatment requires prolonged courses (4–8 weeks) of antibiotics that penetrate the prostate well. The fluoroquinolones, tetracyclines and macrolides have the best penetration. There have been contradictory findings regarding the penetrability of nitrofurantoin , quinolones (ciprofloxacin, levofloxacin), sulfas (Bactrim, Septra), doxycycline and macrolides (erythromycin, clarithromycin). This is particularly true for gram-positive infections.

In a review of multiple studies, Levofloxacin (Levaquin) was found to reach prostatic fluid concentrations 5.5 times higher than Ciprofloxacin, indicating a greater ability to penetrate the prostate.

Persistent infections may be helped in 80% of patients by the use of alpha blockers (tamsulosin (Flomax), alfuzosin), or long term low dose antibiotic therapy. Recurrent infections may be caused by inefficient urination (benign prostatic hypertrophy, neurogenic bladder), prostatic stones or a structural abnormality that acts as a reservoir for infection.

In theory, the ability of some strains of bacteria to form biofilms might be one factor amongst others to facilitate development of chronic bacterial prostatitis.

Escherichia coli extract and cranberry have a potentially preventive effect on the development of chronic bacterial prostatitis, while combining antibiotics with saw palmetto, lactobacillus sporogens and arbutin may lead to better treatment outcomes.

Bacteriophages hold promise as another potential treatment for chronic bacterial prostatatis.

The addition of prostate massage to courses of antibiotics was previously proposed as being beneficial and prostate massage may mechanically break up the biofilm and enhance the drainage of the prostate gland. However, in more recent trials, this was not shown to improve outcome compared to antibiotics alone.

If symptomatic, testing is recommended. The risk of contracting Micoplasma infection can be reduced by the following:

- Using barrier methods such as condoms

- Seeking medical attention if you are experiencing symptoms suggesting a sexually transmitted infection.

- Seeking medical attention after learning that a current or former sex partner has, or might have had a sexually transmitted infection.

- Getting a STI history from your current partner and insisting they be tested and treated before intercourse.

- Avoiding vaginal activity, particularly intercourse, after the end of a pregnancy (delivery, miscarriage, or abortion) or certain gynecological procedures, to ensure that the cervix closes.

- Abstinence

Mycoplasmas have a triple-layered membrane and lack a cell wall. Commonly used antibiotics are generally ineffective because their efficacy is due to their ability to inhibit cell wall synthesis. Micoplasmas are not affected by penicillins and other antibiotics that act on the cell wall. The growth of micoplasmas in their host is inhibited by other broad-spectrum antibiotics. These broad-spectrum antibiotics inhibit the multiplication of the mycoplasma but does not kill them. Tetracyclines, macrolides, erythromycin, macrolides, ketolides, quinolones are used to treat mycoplasma infections. In addition to the penicillins, mycoplasmas are resistant to rifampicin. Mycoplasmas may be difficult to eradicate from human or animal hosts or from cell cultures by antibiotic treatment because of resistance to the antibiotic, or because it does not kill the mycoplasma cell. Mycoplasma cells are able to invade the cells of their hosts.

Urinary catheters should be inserted using aseptic technique and sterile equipment (including sterile gloves, drape, sponges, antiseptic and sterile solution), particularly in an acute care setting. Hands should be washed before and after catheter insertion. Overall, catheter use should be minimized in all patients, particularly those at higher risk of CAUTI and mortality (e.g. the elderly or those with impaired immunity).

Unfortunately mesna is ineffective as a treatment once hemorrhagic cystitis has developed. Although rare, once a case of radiation-induced hemorrhagic cystitis is diagnosed there is no empirically-proven treatments to heal this type of condition, which can severely degrade a patient's quality of life and might possibly lead to renal failure with risk of death.

Viral hemorrhagic cystitis in children generally spontaneously resolves within a few days.

The first step in the treatment of HC should be directed toward clot evacuation. Bladder outlet obstruction from clots can lead to urosepsis, bladder rupture, and renal failure. Clot evacuation can be performed by placing a wide-lumen bladder catheter at bedside. The bladder can be irrigated with water or sodium chloride solution. The use of water is preferable because water can help with clot lysis. Care must be taken to not overdistend the bladder and cause a perforation.. Hyperbaric oxygen (HBO2) therapy has been proven to be effective in treating radiation-induced hemorrhagic cystitis.

In a small minority of cases of urethral syndrome, treatment with antibiotics is effective, which indicates that in some cases it may be caused by bacterial infection which does not show up in either urinalysis or urine culture. For chronic urethral syndrome, a long term, low-dose antibiotic treatment is given on a continuous basis or after intercourse each time if intercourse appears to trigger symptoms.

As low oestrogen may also be considered a source for urethral syndrome, hormone replacement therapy, and oral contraceptive pill (birth-control pills) containing oestrogen are also used to treat the symptoms of this condition in women.

Bladder instillation of medication is one of the main forms of treatment of interstitial cystitis, but evidence for its effectiveness is currently limited. Advantages of this treatment approach include direct contact of the medication with the bladder and low systemic side effects due to poor absorption of the medication. Single medications or a mixture of medications are commonly used in bladder instillation preparations. DMSO is the only approved bladder instillation for IC/BPS yet it is much less frequently used in urology clinics.

A 50% solution of DMSO had the potential to create irreversible muscle contraction. However, a lesser solution of 25% was found to be reversible. Long-term use of DMSO is questionable, as its mechanism of action is not fully understood though DMSO is thought to inhibit mast cells and may have anti-inflammatory, muscle-relaxing, and analgesic effects. Other agents used for bladder instillations to treat interstitial cystitis include: heparin, lidocaine, chondroitin sulfate, hyaluronic acid, pentosan polysulfate, oxybutynin, and botulinum toxin A. Preliminary evidence suggests these agents are efficacious in reducing symptoms of interstitial cystitis, but further study with larger, randomized, controlled clinical trials is needed.

Diet modification is often recommended as a first-line method of self-treatment for interstitial cystitis, though rigorous controlled studies examining the impact diet has on interstitial cystitis signs and symptoms are currently lacking. Individuals with interstitial cystitis often experience an increase in symptoms when they consume certain foods and beverages. Avoidance of these potential trigger foods and beverages such as caffeine-containing beverages including coffee, tea, and soda, alcoholic beverages, chocolate, citrus fruits, hot peppers, and artificial sweeteners may be helpful in alleviating symptoms. Diet triggers vary between individuals with IC; the best way for a person to discover his or her own triggers is to use an elimination diet. Sensitivity to trigger foods may be reduced if calcium glycerophosphate and/or sodium bicarbonate is consumed. The foundation of therapy is a modification of diet to help patients avoid those foods which can further irritate the damaged bladder wall.

The mechanism by which dietary modification benefits people with IC is unclear. Integration of neural signals from pelvic organs may mediate the effects of diet on symptoms of IC.

A number of medications can be used to treat this disorder. Alpha blockers and/or antibiotics appear to be the most effective with NSAIDs such as ibuprofen providing lesser benefit.

- Treatment with antibiotics is controversial. Some have found benefits in symptoms while others have questioned the utility of a trial of antibiotics. Antibiotics are known to have anti-inflammatory properties and this has been suggested as an explanation for their partial efficacy in treating CPPS. Antibiotics such as fluoroquinolones, tetracyclines, and macrolides have direct anti-inflammatory properties in the absence of infection, blocking inflammatory chemical signals (cytokines) such as interleukin-1 (IL-1), interleukin-8 and tumor necrosis factor (TNF), which coincidentally are the same cytokines found to be elevated in the semen and EPS of men with chronic prostatitis.

- The effectiveness of alpha blockers (tamsulosin, alfuzosin) is questionable in men with CPPS. A 2006 meta-analysis found that they are moderately beneficial when the duration of therapy was at least 3 months.

- An estrogen reabsorption inhibitor such as mepartricin improves voiding, reduces urological pain and improves quality of life in patients with chronic non-bacterial prostatitis.

- Therapies that have not been properly evaluated in clinical trials although there is supportive anecdotal evidence include gabapentin, benzodiazepines, and amitriptyline.

Even when caught early, aggressive treatment is required (Bobba). Antibiotics are proven to cure Emphysematous cystitis over time and reduce the amount of gas inside the bladder wall. Prognosis is poor if antibiotics are not used to treat the patient. Additional treatment consists of urinary drainage and good control of blood glucose. The treatment of underlying comorbid diseases, such as diabetes, is extremely important because they can intensify the infection (Gheonea, Bondari). Hyperbaric oxygen is an effective treatment, and has cured some cases in as little as 48 hours. Although it is unclear as to how gas formation occurs in emphysematous cystitis, it’s dependant on whether or not the patient has contributing diseases (Mccabe). Gas formation in diabetic patients diagnosed with Emphysematous cystitis has been determined to occur due to the production of carbon dioxide as a result of the fermentation of the high concentrations of glucose. Gas formation in nondiabetic patients is most likely due the breaking down of urinary lactulose and tissue proteins. Inflammation caused by infection increases pressure and decreases circulation, which provides the perfect environment for bacteria to produce gas (Sereno).

Transurethral needle ablation of the prostate (TUNA) has been shown to be ineffective in trials.

Bacteria and yeast, including those naturally occurring as part of the human microbiome, can travel along urinary catheters and cause an infection in the bladder, kidneys, and other organs connected to the urinary tract.

CAUTI can lead to complications such as prostatitis, epididymitis, and orchitis in men, and cystitis, pyelonephritis, gram-negative bacteremia, endocarditis, vertebral osteomyelitis, septic arthritis, endophthalmitis, and meningitis in all patients. Complications associated with CAUTI cause discomfort to the patient, prolonged hospital stay, and increased cost and mortality. It has been estimated that more than 13,000 deaths are associated with UTIs annually. Estimated > 560,000 nosocomial UTIs annually.

The 5α-reductase inhibitors finasteride and dutasteride may also be used in men with BPH. These medications inhibit the 5α-reductase enzyme, which, in turn, inhibits production of DHT, a hormone responsible for enlarging the prostate. Effects may take longer to appear than alpha blockers, but they persist for many years. When used together with alpha blockers, no benefit was reported in short-term trials, but in a longer term study (3–4 years) there was a greater reduction in BPH progression to acute urinary retention and surgery than with either agent alone, especially in patients were more severe symptoms and larger prostates. Other trials have confirmed reductions in symptoms, within 6 months in one trial, an effect that was maintained after withdrawal of the alpha blocker. Side effects include decreased libido and ejaculatory or erectile dysfunction. The 5α-reductase inhibitors are contraindicated in pregnant women because of their teratogenicity due to interference with fetal testosterone metabolism, and as a precaution, pregnant women should not handle crushed or broken tablets.

Antimuscarinics such as tolterodine may also be used, especially in combination with alpha blockers. They act by decreasing acetylcholine effects on the smooth muscle of the bladder, thus helping control symptoms of an overactive bladder.

Phosphodiesterase-5 inhibitors such as sildenafil citrate show some symptomatic relief, suggesting a possible common cause with erectile dysfunction. Tadalafil was considered then rejected by NICE in the UK for the treatment of symptoms associated with BPH. In 2011, the U.S. Food and Drug Administration approved tadalafil to treat the signs and symptoms of benign prostatic hyperplasia, and for the treatment of BPH and erectile dysfunction (ED), when the conditions occur simultaneously.

Treatment involves avoiding the trigger if that can be determined.

The primary treatment for urethral diverticulum is surgical. The surgery is conducted transvaginally, usually when there is no acute inflammation to better aid dissection of the delicate tissues.

In addition to traditional IC therapies, diet modification remains a core self care strategy as foods that are irritating to the bladder dramatically worsen the symptoms that patients may experience. Foods high in acid and/or caffeine (such as all coffees, regular teas, green teas, sodas, diet sodas, artificial sweeteners and most fruit juices) should be avoided. The daily goal of patients should be to soothe rather than irritate the bladder wall.

Signs indicative of urethral syndrome include a history of chronic recurrent urinary tract infections (UTI) in the absence of both conventional bacterial growth and pyuria (more than 5 white blood cells per High Power Field). Episodes are often related to sexual intercourse.

Some physicians believe that urethral syndrome may be due to a low grade infection of the Skene's glands on the sides and bottom of the urethra. The Skene's glands are embryologically related to the prostate gland in the male, thus urethral syndrome may share a comparable cause with chronic prostatitis.

Possible non-infective causes include hormonal imbalance, trauma, allergies, anatomical features such as diverticula, and post-surgical scarring and adhesions.