Virtually all patients treated with androgen deprivation eventually develop progressive clinical or biochemical disease despite this therapy. Despite low levels of androgen, the androgen receptor remains active, making secondary hormonal therapies a reasonable clinical approach. Considerations for such patients include antiandrogen withdrawal, sequential use of antiandrogens, adrenal cortex inhibitors, and estrogenic compounds. Collectively, the modest activity of these therapies challenges the notion that advancing prostate cancer will uniformly become "hormone refractory."