Targeting AIPC with therapies that affect the mechanisms of androgen receptor signaling despite a castrate testosterone milieu is an active and growing area of clinical research. At present, for patients with AIPC, the data support the maintenance of the castrate state, recognition of the AAWD phenomenon,the sequential use of oral antiandrogens, and a trial of estrogens or adrenal androgen-targeted therapies. Novel agents are being developed that seek to prolong the duration of clinical responses and the overall response rate.