PURPOSE OF REVIEW: In a large proportion of advanced prostate cancer patients treated with androgen deprivation therapy, progression of the disease occurs despite low levels of testosterone, termed castration-resistant prostate cancer. This heralds the onset of the lethal form of the disease. Recent investigations into the mechanisms of castration resistance have shown that despite low levels of androgen, the androgen receptor remains active through a variety of mechanisms and thus represents a key treatment target in castration-resistant prostate cancer. RECENT FINDINGS: Clinical approaches to these patients have rapidly progressed and include antiandrogen withdrawal, sequential antiandrogen use, adrenal androgen production inhibitors, and estrogenic compounds. Multiple efforts are underway to develop additional therapies targeted at this phenomenon. SUMMARY: Hormonal therapy in advanced prostate cancer is rapidly evolving to more effectively target disease processes underlying prostate cancer, with multiple promising agents on the horizon.