For patients with advanced prostate cancer, luteinizing hormone-releasing hormone (LHRH) agonists have provided successful androgen deprivation therapy (ADT) for some 25 years. However, the benefits of LHRH agonists are limited in that these agents are agonists, not antagonists. The search for and development of an effective LHRH antagonist have proven difficult. Nevertheless, antagonists offer subtle advantages, including more rapid reduction in testosterone levels, reduction in testosterone-induced flare, and maintenance of castrate levels of testosterone. Accordingly, LHRH antagonists appear to provide a viable alternative to LHRH agonist therapy. Degarelix, a recently approved LHRH antagonist, has been shown to work more quickly in lowering serum testosterone levels, with an acceptable safety profile and a mechanism of action that obviates the testosterone surges associated with LHRH agonist use. Presently, degarelix is the only LHRH antagonist approved for the treatment of advanced prostate cancer.