Over the past 2 decades, MRI has been integrated into the diagnosis of multiple sclerosis (MS), the study of MS pathobiology, and the development and monitoring of MS treatments. This integration has irrevocably changed the way we think about the disease. New treatments, advanced through early stages of development using MRI outcome measures, have revolutionized the treatment of MS. Although MS remains a clinical diagnosis, conventional MRI is now a requisite adjunct to that diagnosis. Early in the disease, MRI monitoring of a patient on immunomodulatory therapy is helpful in identifying breakthrough disease activity that may predict long-term outcome. Advanced MRI technologies, although currently relegated to the research realm, are improving the detection of previously underappreciated aspects of MS pathology and may help lead to the evaluation of new therapeutic strategies.