Prostate cancer is estimated to be the second most common malignancy in men in the USA in 2020 and represents the second highest mortality from cancer behind lung and bronchial neoplasms. Management of advanced prostate cancer is evolving. Medical androgen deprivation therapy is currently a cornerstone of therapy for prostate cancer; however molecular mechanisms of resistance have emerged leading to castration-resistant prostate cancer that is proliferation of prostate cancer in the setting of low testosterone (< 50 ng/dl). The benefit of double androgen blockade like ADT plus abiraterone acetate or androgen receptor blockers is proven in many clinical trials; however multiple mechanisms of resistance still exist. In theory, another layer of androgen blockade will prevent, or at least slow, prostate cancer proliferation. This direction of thought has recently been explored with multiple clinical trials. In this review article, we summarize the current knowledge regarding androgen resistance, newer androgen inhibition therapies, and the implications of a triple-arm anti-androgen blockade in advanced prostate cancer.