The management of patients with evidence of a detectable prostate-specific antigen (PSA) following prostatectomy is an increasingly common and difficult issue for patients and clinicians alike. In the setting in which biochemical failure is believed representative of early systemic failure, therapeutic options primarily involve the use of hormonal therapy. Extrapolating results of early vs. delayed hormonal therapy from studies of patients with more advanced prostate cancer is problematic. Antiandrogen monotherapy and intermittent androgen deprivation are increasingly popular approaches, although their ultimate utility remains unproven. This patient subset is an optimal one in which to conduct clinical trials to both define the role of hormonal therapy and to investigate novel, non-hormonal approaches. The most appropriate therapeutic intervention for patients with evidence of biochemical failure following radical prostatectomy remains undefined.