Among men treated with prostatectomy or radiation therapy for localized prostate cancer, the state of an increasing prostate-specific antigen (PSA) level is known as biochemical recurrence (BCR). BCR can be predictive of the development of subsequent distant metastases and ultimately death, but BCR often predates other signs of clinical progression by several years. Although patients may be concerned about their rising PSA levels, physicians attempting to address patient anxiety must inform them that BCR is not typically associated with imminent death from disease, and that the natural history of biochemical progression may be prolonged. Misinterpretation of the significance of early changes in PSA may cause patients to receive androgen deprivation therapy (ADT) prematurely, especially in settings where the disease is unlikely to impact survival. In addition, knowledge of the morbidities associated with ADT (hot flashes, impotence, sarcopenia, metabolic syndrome, bone loss, and increased risk of vascular disease) has accelerated the search for alternative treatment options for these patients. Clinical trials investigating when and how to best use and supplement hormonal therapies in this patient population are under way, as are trials of novel nonhormonal targeted agents, immunotherapies, natural products, and other pharmaceuticals that have been approved by the US Food and Drug Administration (FDA) for other indications. This review will summarize the acceptable standards of care for the management of biochemically recurrent prostate cancer, and will also outline some novel experimental approaches for the treatment of this disease state.