Huggins and Hodges described the first systemic targeted therapy for prostate cancer in 1941 with their report on the effects of androgen ablation in men with metastatic disease. Since that time, researchers have identified multiple additional "targets" that may be important in prostate cancer tumorigenesis. These areas include continued emphasis on the androgen receptor in the androgen-independent state, parallel growth pathways such as AKT and HER2 that may act in conjunction or independently of the androgen receptor, the supporting environment that allows for the development of metastatic disease, and standard cytotoxic targets, such as the microtubule. This review is intended to highlight these potential targets and several of the agents that are under development in the treatment of prostate cancer.