Guidelines for the management of prostate cancer issued by the National Comprehensive Cancer Network provide a basis for rational treatment decisions. These guidelines represent consensus recommendations by a panel of experts that are evidence based and are designated according to the degree of consensus within the expert panel. The initial stratification point is the patient’s life expectancy (>5 or <5 years). If life expectancy is >5 years, the recommended intervention is based on clinical stage, prostate-specific antigen (PSA) level, and Gleason score, as well as the presence of symptoms. These assessments establish the patient’s risk of recurrence after therapy. Specific initial therapies are then recommended according to whether the risk category is low, intermediate, high, or very high. The guidelines also describe the appropriate use of observation (“watchful waiting”) versus active intervention in certain patients. After definitive therapy, patients should be monitored with PSA determinations, digital rectal examination, and bone scans, as outlined in the guidelines. Patients who exhibit increasing PSA levels after prostatectomy are candidates for salvage therapy with androgen ablation, radiotherapy, or observation. If PSA levels begin to increase after radiotherapy, surgery may then be an additional option. Systemic salvage therapy generally consists of androgen ablation; the benefit of total androgen blockade versus initial monotherapy remains controversial. Relapse after initial androgen ablation is treated with an antiandrogen, if none had been administered previously. Patients refractory to further hormonal manipulations are observed or receive palliative therapy, including chemotherapy. The treatment of prostate cancer is complex. Optimal treatment is risk-adapted to the specific characteristics of the cancer and the expected longevity and personal preferences of the patient.