This article summarizes the historical perspective of clinical trials in androgen independent prostate cancer. In October of 2004, the results from TAX 327 and SWOG 9916, two large, randomized, phase III trials, independently confirmed that every-3-week docetaxel-based therapy produces a modest survival benefit and immediately established docetaxel as first-line standard treatment. These trials reported the first survival benefit from cytotoxic therapy seen in the treatment of AIPC and led to the FDA approval of docetaxel in this setting. Multiple clinical trials are ongoing in attempts to extend the survival benefits gained from docetaxel in AIPC and to define the role of cytotoxic therapy in earlier stages of disease. Improved collaboration between medical and urologic oncologists is essential to facilitate clinical trial enrollment so that answers can be learned to important clinical questions regarding optimal management of all stages of disease.