Despite efforts at early detection with prostate specific antigen-based screening, more than 25,000 patients in the United States will die this year of metastatic prostate cancer. As a consequence both of screening and increased use of androgen deprivation therapy, patients commonly present with low volume, asymptomatic, metastatic disease. Over the past 2 decades chemotherapy for advanced prostate cancer has evolved from a frightful, toxic experience to one that frequently provides clinically meaningful palliation and a modest, but real survival benefit. With the establishment of docetaxel-based chemotherapy as initial therapy, efforts are underway to evaluate the role of second-line systemic therapy options.