Hormone refractory prostate cancer (HRPC) is a difficult clinical problem. These patients are intolerant of aggressive cytotoxic therapies because of their age and poor performance status. Systemic chemotherapy, whether administered as single agents or in multidrug combinations, has not been shown to prolong survival. It is only recently that palliative endpoints, such as quality of life analyses, have been formally evaluated in the clinical trials of HRPC. As a result, mitoxantrone plus prednisone has been demonstrated to be a useful palliative therapy that provides improvements in pain and quality of life for approximately 40% of those treated. Other promising regimens, such as the estramustine combinations or docetaxel, are currently undergoing phase III trials designed to prove superiority to mitoxantrone plus prednisone. Suramin has been extensively studied, but due to its poor activity seen in recent randomized trials, as well as the toxicity and inconvenience, it will likely not be further developed in HRPC. In recent years, there has been a tremendous increase in the development of biological targets for cancer therapy and a number of these are in early trials for HRPC. Given the relative insensitivity of prostate cancer to cytotoxic agents, this area holds much potential.