At present, the management of non-organ confined prostate cancer, whether it is a recurrence or metastasis, continues to evolve based on prostate cancer detection using prostate-specific antigen and the development of medications as alternatives for the classical orchiectomy, which induced irreversible implications for quality of life. Diethylstilbestrol therapy was associated with cardiovascular side-effects; GnRH agonists were able to create a castration level, but again considerable side-effects were described. Combination therapies using antiandrogens and GnRH agonists do not improve survival and have additional toxicity. GnRH antagonists, which also suppress FSH, represent the latest class of agents introduced for hormonal treatment, but phase III studies with survival data are not yet available. In spite of all these achievements, hormonal manipulation has resulted in only modest improvements during recent decades and new targets are needed to improve the clinical outcome. Selectively modifying the androgen receptor is currently one of the most promising developments.