Androgen deprivation as a treatment for prostate cancer has evolved since the pioneering studies of Huggins and Hodges 60 years ago using surgical castration or estrogen treatments. The most common hormonal treatments today use injections of luteinizing hormone-releasing hormone (LHRH) agonists. The US Food and Drug Administration (FDA) has approved 5 LHRH agonist formulations for treatment of prostate cancer in the United States. Of these approved products, 3 involve different delivery systems for the LHRH superagonist leuprolide acetate. Sustained-release formulations of 2 distinct LHRH agonists, goserelin acetate and triptorelin pamoate, are also commercially available. This review focuses on new data on a novel formulation of leuprolide acetate (Eligard; Atrix Laboratories Inc., Fort Collins, CO) that incorporates a unique mixture of selected polymers and solvents to achieve sustained drug delivery after subcutaneous injection. The FDA has approved 1-month and 3-month formulations of Eligard, and 4-month and 6-month products are in development. In clinical trials, Eligard achieves reliable and sustained suppression of serum testosterone to castration levels (< or =50 ng/dL). Of the patients treated with the 1-month and 3-month formulations, 98% (115 of 117) and 94% (104 of 111), respectively, reached testosterone levels of < or =20 ng/dL. Breakthroughs, defined as testosterone levels >50 ng/dL after achievement of castration levels, occurred rarely at 0% (0 of 117) for the 1-month and at 0.9% (1 of 111) for the 3-month formulations in patients receiving Eligard. The degree of disease control and the adverse-events profile are commensurate with the effectiveness of the testosterone suppression; the incidence of severe hot flashes is actually lower than anticipated. Additional studies with these novel formulations are warranted.