New therapeutic strategies are needed to improve treatment outcomes in men with hormone-refractory prostate cancer. A better understanding of the molecular mechanisms of cell death in response to therapeutic strategies will help avoid ineffective treatment regimens and provide a molecular basis for new therapeutic modalities targeting apoptosis-resistant forms of prostate cancer. In this review, the authors focused on the established aberrations of apoptosis in hormone-refractory prostate cancer, and they have described novel treatment strategies to overcome apoptosis resistance.