While docetaxel/prednisone chemotherapy has demonstrated a survival advantage in metastatic hormone refractory prostate cancer (HRPC) patients, the optimal duration of chemotherapy has not yet been established. Currently, a standard practice is to treat patients indefinitely until unacceptable toxicity or disease progression. A systematic approach to providing breaks in treatment schedules (intermittent chemotherapy) for patients who experience an initial response to chemotherapy may avoid or delay the development of progressive toxicity. Whether continuous therapy offers an advantage over intermittent therapy, in terms of balancing disease control and overall survival with treatment-related toxicities and quality-of-life (QOL) is yet unanswered. This article will: (1) review the data from prior studies of intermittent versus continuous chemotherapy in other solid tumors, (2) review existing trials of intermittent chemotherapy in prostate cancer, (3) discuss intermittent chemotherapy clinical trial design considerations, and (4) discuss the future role of intermittent chemotherapy for the treatment of prostate cancer.