Prostate cancer recurrence (after prior local treatment) that is detectable only by a rise in serum prostate specific antigen (PSA) level is a very common problem facing clinicians. Given that the majority of contemporary era men with PSA-only or biochemical recurrence are relatively young and otherwise healthy, treatment requires approaches that both improve clinical outcomes and preserve quality of life. Treatment is in one of two broad categories, additional local therapies, termed "salvage" local therapy and systemic therapies. For radical prostatectomy patients, salvage external beam radiotherapy to the prostate bed is commonly employed, being reserved for early biochemical recurrence in men with low risk at distant metastases. For primary radiation patients, salvage radical prostatectomy or cryotherapy can similarly be used for those men felt not to harbor distant metastases. Systemic therapy generally involves hormonal therapy. Traditional hormonal therapy (orchiectomy, luteinizing hormone-releasing hormone agonists or maximum androgen blockade) is the current mainstay of systemic treatment for biochemical recurrence, although non-traditional approaches, such as antiandrogen monotherapy, are increasingly being used. There is a critical need for new pharmaceutical agents to treat this growing stage of prostate cancer. However, it has been difficult to demonstrate efficacy due to the long natural history until death and the survival endpoint currently required by the U.S. Food and Drug Administration. New data show that PSA Doubling time (PSA-DT) during PSA recurrence may be a valid surrogate for death from the disease and may be used to accelerate drug approval. This monograph will attempt to provide a complete balanced discussion of the evaluation and treatment of biochemical recurrence of prostate cancer after prior primary local therapy.