Heidi Crayton, MD, and Maria Lopes, MD, discuss the impact of multiple sclerosis on patients, families, and caregivers, differentiate relapsing forms (relapsing-remitting and primary progressive) from non-relapsing forms (non-relapsing secondary progressive) in clinical practice, and highlight the key pathophysiological features of relapsing multiple sclerosis and the impact of progression independent of relapse activity (PIRA) after an initial demyelinating event.