Prostate-specific antigen increasingly is being used as a surrogate end point in trials of new agents in patients with hormone refractory prostate cancer. This article reviews data that support this marker as a surrogate end point and the contradictory data reported recently for trials of suramin. These contrasting views may originate in the different mechanisms of actions of the agents studied. These data suggest that a decline in prostate-specific antigen of at least 50% from baseline may be an important predictor of survival for patients receiving cytotoxic therapy.