Prostate cancer is the second leading cause of cancer-related deaths in men in most western countries. New agents for metastatic castration-resistant prostate cancer (CRPC) developed in the past 3 years include abiraterone acetate (AA) and enzalutamide (ENZ), which inhibit signaling by and synthesis of androgens, respectively. Because they share the same target, potential clinical cross-resistance between AA and E is possible. In this review, we discuss the results of clinical studies in which CRPC patients were treated with AA and E either separately or in sequence after first-line treatment with docetaxel. Our review suggests that sequential administration of AA and E in either order has limited activity after docetaxel therapy. Prospective studies that further examine sequential treatments with AA and E are warranted.