The survival benefit demonstrated by docetaxel-based therapy in two randomized trials, Southwest Oncology Group (SWOG) 99-16 and TAX 327, has changed the perception of chemotherapy in men with hormone-refractory prostate cancer from nihilism to optimism. These survival improvements are of similar magnitude to those found in trials that established chemotherapeutic regimens for metastatic breast, lung, or colorectal cancer. The timing of chemotherapy in the aforementioned solid tumors is much more clearly defined than in men with metastatic prostate cancer. Traditionally, chemotherapy in men with hormone-resistant prostate cancer was reserved for symptomatic patients only; the inclusion of symptomatic and asymptomatic patients in SWOG 99-16 and TAX 327 has raised several questions regarding the optimal use of chemotherapy in these patients. When is the best time to initiate docetaxel-based chemotherapy? Is it appropriate to use chemotherapy in high-risk patients as adjuvant therapy? Although retrospective analysis of current trials may provide hypothesis, only properly designed randomized clinical trials will answer these questions.