Androgen receptor (AR) signaling is a key pathway in prostate cancer, and patients are initially treated with androgen deprivation therapy. Patients who have stopped responding to androgen deprivation therapy are considered to have castration-resistant prostate cancer (CRPC), which is still dependent on AR signaling. Enzalutamide, an orally available AR inhibitor, was initially approved by the US FDA for the treatment of patients with metastatic CRPC who have previously received docetaxel. The indication was subsequently extended to include all patients with metastatic CRPC, and most recently to include patients with nonmetastatic CRPC. This review summarizes the body of evidence supporting enzalutamide efficacy and safety in CRPC.