Enzalutamide (Xtandi(®)) is an androgen receptor inhibitor that blocks several steps in the androgen receptor signalling pathway. This article reviews the clinical efficacy and tolerability of oral enzalutamide in chemotherapy-naïve men with metastatic castration-resistant prostate cancer (CRPC), as well as summarizing its pharmacological properties. In the randomized, double-blind, multinational PREVAIL trial, enzalutamide significantly improved both radiographic progression-free survival and overall survival versus placebo in chemotherapy-naïve men with metastatic CRPC who were asymptomatic or mildly symptomatic. In addition, enzalutamide significantly delayed the need for chemotherapy and the decline in health-related quality of life versus placebo. Enzalutamide was generally well tolerated in chemotherapy-naïve men with metastatic CRPC. In conclusion, enzalutamide is a convenient, effective and well tolerated treatment for chemotherapy-naïve men with metastatic CRPC who are asymptomatic or mildly symptomatic.