Prostate cancer is the most frequently diagnosed cancer and the second leading cause of cancer death in men, following lung cancer. Although radical prostatectomy continues to be a curative treatment for most patients diagnosed with prostate cancer, nearly 25% of patients undergoing radical prostatectomy will have biochemical recurrence as defined by an increase in serum prostate-specific antigen (PSA) level to >0.4 ng/mL after prostatectomy or a rapid doubling of the PSA over a 10-year follow-up period. The clinical challenges, an overview of available data, and a framework for the integration of this information for clinical management of biochemical recurrence postprostatectomy for prostate carcinoma are presented in this article. Therapeutic options, in addition to conservative management and watchful waiting, include radiation therapy and androgen deprivation. These options are discussed herein along with expected outcomes.