Research into therapeutic applications of apheresis is limited by the rarity of many of the diseases for which plasma exchange (PLEX) is indicated. PLEX has now become a widely used treatment in select patients with acute relapses of inflammatory demyelinating disease in a variety of contexts including multiple sclerosis (MS). Natalizumab inhibits central nervous system (CNS) lymphocyte trafficking by blocking alpha4-integrin, and its serological clearance is enhanced by PLEX. Circulating pathologic antibodies directed against myelin oligodendrocyte glycoprotein and myelin basic protein have been implicated in subsets of MS patients. Complications occur in 4.75% to 36% of PLEX procedures. The majority are mild, easily treated, and self-limited and include paresthesias and muscle cramping due to hypocalcemia from citrate anticoagulant, bleeding and hematoma formation from vascular access, urticaria/pruritus and fever from blood products, hypotension, pallor, nausea, and vomiting.