The management of metastatic prostate cancer not previously treated with androgen deprivation therapy (ADT) has undergone a paradigm shift in the past 5 years. In addition to commencing ADT, there are multiple phase 3 clinical trials showing that the addition of docetaxel chemotherapy or novel hormonal agents (abiraterone acetate, enzalutamide, apalutamide) significantly improves overall survival. Intensification of systemic therapy is now the standard of care for newly diagnosed metastatic prostate cancer but many challenges remain including optimal selection of patients, management of additional toxicity, and the development of adaptive resistance.