Corticosteroids have been used in the management of prostate cancer for over 30 years. Although daily oral corticosteroids have frequently used in conjunction with chemotherapy for metastatic castration-resistant prostate cancer, their independent impact on survival is unclear. However, corticosteroids confer palliative benefits and are associated with objective responses and circulating tumor cell (CTC) and PSA declines in a small minority of patients, although toxicities such as osteoporosis and immunosuppression complicate long-term use. Following the demonstration of a palliative benefit for mitoxantrone combined with corticosteroids compared with corticosteroids alone, subsequent trials that demonstrated a benefit for first-line docetaxel over mitoxantrone, and second-line cabazitaxel over mitoxantrone, administered concurrent daily oral corticosteroids with all of these agents to maintain uniformity. Conversely, improved outcomes were demonstrated with docetaxel without corticosteroids for metastatic castration-sensitive prostate cancer. Daily oral corticosteroids are routinely combined with abiraterone to mitigate symptoms of mineralocorticoid excess. In contrast daily corticosteroids are not essential when administering enzalutamide or radium-223, and there is a concern of deleterious immune effects concurrently with sipuleucel-T. Given emerging evidence for promotion of resistance mechanisms, routine administration of daily oral corticosteroids in settings other than abiraterone administration and palliation of symptoms is probably not required.