Surgery is the most common treatment for cancer of the urethra. One of the following types of surgery may be done: Open excision, Electro-resection with flash, Laser surgery, Cystourethrectomy, Cystoprostatectomy, Anterior body cavity, or Incomplete or basic penectomy surgery.

Chemotherapy is sometimes used to destroy urethral cancer cells. It is a systemic urethral cancer treatment (i.e., destroys urethral cancer cells throughout the body) that is administered orally or intravenously. Medications are often used in combination to destroy urethral cancer that has metastasized. Commonly used drugs include cisplatin, vincristine, and methotrexate.

Side effects include anemia (causing fatigue, weakness), nausea and vomiting, loss of appetite, hair loss, mouth sores, increased risk for infection, shortness of breath, or excessive bleeding and bruising.

Treatment methods include surgery, chemotherapy, radiation therapy and medication.

Between 1988 and 2001 in the United States, cancer surveillance reports to SEER included 1,333 cases of ureteral cancer in adults: 808 male and 525 female, 1,158 white and 42 black. Of the total, 1,251 (94%) were transitional cell carcinoma of the papillary type. "Five-year relative survival rates from cancers of the ureter were similar among males vs. females..."

There are several treatment options for penile cancer, depending on staging. They include surgery, radiation therapy, chemotherapy, and biological therapy. The most common treatment is one of five types of surgery:

- Wide local excision—the tumor and some surrounding healthy tissue are removed

- Microsurgery—surgery performed with a microscope is used to remove the tumor and as little healthy tissue as possible

- Laser surgery—laser light is used to burn or cut away cancerous cells

- Circumcision—cancerous foreskin is removed

- Amputation (penectomy)—a partial or total removal of the penis, and possibly the associated lymph nodes.

Radiation therapy is usually used adjuvantly with surgery to reduce the risk of recurrence. With earlier stages of penile cancer, a combination of topical chemotherapy and less invasive surgery may be used. More advanced stages of penile cancer usually require a combination of surgery, radiation and chemotherapy.

In addition to all the above, treatment of the underlying disease like brucellosis, is important to limit disease recurrence.

Urethral cancer is cancer originating from the urethra. Cancer in this location is rare, and the most common type is papillary transitional cell carcinoma. The most common site of urethral cancer is the bulbomembranous urethra.

Prognosis can range considerably for patients, depending where on the scale they have been staged. Generally speaking, the earlier the cancer is diagnosed, the better the prognosis. The overall 5-year survival rate for all stages of penile cancer is about 50%.

Certain medications can increase urination difficulties by increasing bladder outlet resistance by increasing smooth muscle tone at the prostate or bladder neck and contribute to LUTS. Alpha-adrenergic agonist medications, such as decongestants with pseudoephedrine can increase bladder outlet resistance. In contrast, calcium channel blockers and anticholinergic medications can worsen urinary retention by promoting bladder muscle relaxation. Diuretic medications such as loop diuretics (e.g., furosemide) or thiazides (e.g., chlorthalidone) can cause or worsen urinary frequency and nighttime awakenings to urinate.

Lifestyle alterations to address the symptoms of BPH include physical activity, decreasing fluid intake before bedtime, moderating the consumption of alcohol and caffeine-containing products and following a timed voiding schedule. Patients can also attempt to avoid products and medications with anticholinergic properties that may exacerbate urinary retention symptoms of BPH, including antihistamines, decongestants, opioids, and tricyclic antidepressants; however, changes in medications should be done with input from a medical professional.

The main treatment for isolated epispadias is a comprehensive surgical repair of the genito-urinary area usually during the first 7 years of life, including reconstruction of the urethra, closure of the penile shaft and mobilisation of the corpora. The most popular and successful technique is known as the modified Cantwell-Ransley approach. In recent decades however increasing success has been achieved with the complete penile disassembly technique despite its association with greater and more serious risk of damage.

Anterior urethral cancer is a disease in which malignant cancer cells are found in the part of the urethra that is closest to the outside of the body.

It is also known that disruption of the endocrine system by certain chemicals adversely affects the development of the reproductive system and can cause vaginal cancer. Many other reproductive diseases have also been link to exposure to synthetic and environmental chemicals. Common chemicals with known links to reproductive disorders include: lead, dioxins and dioxin-like compounds, styrene, toluene, BPA (Bisphenol A) and pesticides.

Even with successful surgery, patients may have long-term problems with:

- incontinence, where serious usually treated with some form of continent urinary diversion such as the Mitrofanoff

- depression and psycho-social complications

- sexual dysfunction

A permanent urethral stent was approved for use in men with bulbar urethral strictures in 1996, but was recently removed from the market.

A temporary thermoexpandable urethral stent (Memotherm) is available in Europe, but is not currently approved for use in the United States.

Left untreated, urethral diverticulum can cause significant morbidity (sickness).

During surgery, there is a risk for complications due to the highly vascular nature of the tissue. The urethral sphincters and its smooth muscle, as well as the neck of the bladder, can be injured regardless of the surgical approach. Other complications from surgery can include urinary incontinence, stress incontinence, a urethrovaginal fistula, or recurrent diverticula. Horseshoe-shaped diverticula and diverticula that completely surround the urethra are both associated with worse outcomes, as are those located close to the bladder, and large (over 3–4 cm) diverticula.

Permanent stents are often metal coils, which are inserted into the male urethra. The braided mesh is designed to expand radially, applying constant gentle pressure to hold open the sections of the urethra that obstruct the flow of urine. The open, diamond-shape cell design of the stent allows the stent to eventually become embedded in the urethra, thus minimizing the risk for encrustation and migration. Permanent stents are used to relieve urinary obstructions secondary to benign prostatic hyperplasia (BPH), recurrent bulbar urethral stricture (RBUS), or detrusor external sphincter dyssynergia (DESD). The main motive for removal of permanent stents is worsening of symptoms even with device fitted. Other reasons have been migration, clot retention, hematuria, and urinary retention. The only FDA approved permanent stent is the Urolume. Usually, permanent stents are used only for men who are unwilling or unable to take medications or who are reluctant or unable to have surgery. Most doctors do not consider permanent stents a viable long-term treatment for most men.

The use of bioengineered urethral tissue is promising, but still in the early stages. The Wake Forest Institute of Regenerative Medicine has pioneered the first bioengineered human urethra, and in 2006 implanted urethral tissue grown on bioabsorbable scaffolding (approximating the size and shape of the affected areas) in five young (human) males who suffered from congenital defects, physical trauma, or an unspecified disorder necessitating urethral reconstruction. As of March, 2011, all five recipients report the transplants have functioned well.

There are two types of prostatic stent: temporary and permanent.

Although a permanent prostatic stent is not a medical treatment, it falls under the classification of a surgical procedure. Placement of a permanent prostatic stent is carried out as an outpatient treatment under local, topical or spinal anesthesia and usually takes about 15–30 minutes.

A temporary prostatic stent can be inserted in a similar manner to a Foley catheter, requiring only topical anesthesia.

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.

Paraphimosis can be avoided by bringing the foreskin back into its normal, forward, non-retracted position after retraction is no longer necessary (for instance, after cleaning the glans penis or placing a Foley catheter). Phimosis (both pathologic and normal childhood physiologic forms) is a risk factor for paraphimosis; "physiologic" phimosis resolves naturally as a child matures, but it may be advisable to treat "pathologic" phimosis via long-term stretching or elective surgical techniques (such as preputioplasty to loosen the preputial orifice or circumcision to amputate the foreskin tissue partially or completely).

The foreskin responds to the application of tension to cause expansion by creating new skin cells though the process of mitosis. The tissue expansion is permanent. Non-surgical stretching of the foreskin may be used to widen a narrow, non-retractable foreskin. Stretching may be combined with the use of a steroid cream. Beaugé recommends manual stretching for young males in preference to circumcision as a treatment for non-retractile foreskin because of the preservation of sexual sensation.

Paraphimosis can often be effectively treated by manual manipulation of the swollen foreskin tissue. This involves compressing the glans and moving the foreskin back to its normal position, perhaps with the aid of a lubricant, cold compression, and local anesthesia as necessary. If this fails, the tight edematous band of tissue can be relieved surgically with a dorsal slit or circumcision. An alternative method, the Dundee technique, entails placing multiple punctures in the swollen foreskin with a fine needle, and then expressing the edema fluid by manual pressure. According to Ghory and Sharma, treatment by circumcision may be elected as "a last resort, to be performed by a urologist". Other experts recommend delaying elective circumcision until after paraphimosis has been resolved.

Congenital anomalies like cryptorchidism, renal agenesis/dysplasia, musculoskeletal and cardiopulmonary anomalies are also common (>50% cases), hence evaluation of the patient for internal anomalies is mandatory.

Although aphallia can occur in any body type, it is considered a substantially more troublesome problem with those who have testes present, and has in the past sometimes been considered justification for assigning and rearing a genetically male infant as a girl. After the theory in the 1950s that gender as a social construct was purely nurture and so an individual child could be raised early on and into one gender or the other regardless of their genetics or brain chemistry. Intersex people generally advocate harshly against coercive genital reassignment however, and encourage infants to be raised choosing their own gender identity. The nurture theory has been largely abandoned and cases of trying to rear children this way have not proven to be successful transitions.

In newborn period or infancy, feminizing operations are recommended for treatment of penile agenesis, but after 2 years, as sexual identification of the patients has appeared, it is advised to perform masculinizing operations in order not to disturb the child psychologically.

Recent advances in surgical phalloplasty techniques have provided additional options for those still interested in pursuing surgery.

Webbed penis, also called penis palmatus or penoscrotal fusion, is an acquired or congenital condition in which the scrotal skin extends onto the ventral penile shaft. The penile shaft is buried in scrotum or tethered to the scrotal midline by a fold or web of skin. The urethra and erectile bodies are usually normal. Webbed penis is usually asymptomatic, but the cosmetic appearance is often unacceptable. This condition may be corrected by surgical techniques.

In the congenital form, the deformity represents an abnormality of the attachment between the penis and the scrotum; the penis, the urethra, and the remainder of the scrotum typically are normal.

Webbed penis may also be acquired (iatrogenic) after circumcision or other penile surgery, resulting from excessive removal of ventral penile skin; the penis can retract into the scrotum, resulting in secondary phimosis (trapped penis).

One procedure for webbed penis is the insertion of a subcutaneous soft silicone implant under the penile skin. The procedure was developed by urologist James J. Elist.

A Gartner's duct cyst (sometimes incorrectly referred to as "vaginal inclusion cyst") is a benign vaginal cystic lesion that arises from the Gartner's duct, which is a vestigial remnant of the mesonephric duct (wolffian duct) in females. They are typically small asymptomatic cysts that occur along the lateral walls of the vagina, following the course of the duct. They can present in adolescence with painful menstruation (Dysmenorrhea) or difficulty inserting a tampon. They can also enlarge to substantial proportions and be mistaken for urethral diverticulum or other structures.

There is a small association between Gartner's duct cysts and metanephric urinary anomalies, such as ectopic ureter & ipsilateral renal hypoplasia. Because of this, imaging is recommended before excision.

Procedure for buried penis is the insertion of a subcutaneous soft silicone implant under the penile skin. The procedure was developed by urologist James J. Elist.

The principal treatment of chordee is surgery in infancy, usually by a pediatric urologist. With chordees caused by circumcision, the preferred method of surgical treatment is a z-plasty. The preferred time for surgery is between the ages of 6 and 18 months and correction is usually successful.

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.