Classically, advanced prostate cancer has been treated with hormonal therapy and, most recently, chemotherapy. This treatment clearly demonstrated a survival benefit, but never a cure. With the ever-expanding understanding of the pathophysiology of prostate cancer, there has been a recent explosion in the potential molecular targets and novel therapeutic approaches to both advanced and potentially localized prostate cancer. This review will focus on what the author perceives to be the most promising of these new strategies. The endothelin pathway has been identified as pivotal in the viscous cycle of tumorigenesis in bone, leading to the development of endothelial receptor antagonists. Vaccine therapy using autologous granulocyte–macrophage colony-stimulating factor-producing prostate cancer cells has been effective in producing both immune and clinical responses. Randomized clinical trials of the immunotherapy cell product APC8015 (Provenge^®) have demonstrated improved survival in the hormone-refractory setting. The development of antisense oligonucleotides to segments of mRNA critical to the progression to androgen-independent disease has emerged as one further tool in the expanding armamentarium of potential therapies being tested. Clearly, headway is being made in improving outcomes in this most prevalent health problem.