Prostate cancer is the second leading cause of death among cancer-affected men. The lifetime risk of developing prostate cancer can be higher than 10%, although the incidence varies widely across races and ethnicity. Increased understanding of the molecular biology of castration-resistant prostate cancer has facilitated the development of alternative treatment approaches for these patients, such as the second-generation androgen receptor antagonists. ARN-509, also known as JNJ-56021927, is an investigational second-generation antiandrogen with high oral bioavailability and long plasma half-life, suggesting once-daily oral dosing. It has shown, additionally, positive results in phase II studies, an excellent safety profile, which makes it well suited as therapy across the entire spectrum of prostate cancer disease states. Currently, ARN-509 is undergoing phase III development, providing a new opportunity to address the unmet needs of patients with advanced prostate cancer.