Magnetic resonance imaging (MRI) of the brain and spinal cord plays a central role in establishing the diagnosis of multiple sclerosis (MS), in monitoring disease activity, and as a key outcome measure in clinical trials of new MS therapies. Conventional MRI continues to evolve, reflecting advances in imaging hardware and software. These advances have led to important new insights into MS disease pathophysiology and can be used to improve patient management. Despite these improvements, standard MRI continues to capture only a small portion of the underlying changes that occur during the course of the disease.