Androgen ablation remains the cornerstone of the systemic management of prostate cancer. After initial androgen deprivation, clinical outcomes vary considerably. For the patient with progressive disease after androgen deprivation, multiple therapeutic options are available and include antiandrogen withdrawal, chemotherapy, and secondary hormonal agents. Multiple secondary hormonal agents have clinical activity and the sequential use of these agents may lead to prolonged periods of clinical response. In addition to the use of oral antiandrogens, active secondary hormonal therapies include adrenolytic agents such as ketoconazole and aminoglutethimide, corticosteroids and estrogenic compounds. This article reviews the clinical trial data for these various agents and discusses their role in the management of patients with advanced prostate cancer.