The objectives of this review are (1) to provide an overview of relapses, (2) to review the pathophysiology of MS with a focus on relapses, (3) to summarize current methods of relapse management, (4) to explore the actions of ACTH via the melanocortin system, and (5) to discuss the relevance of the melanocortin system to MS. Here, POMC is linked to myeloid sarcoma.