Moderate to severe pain is a common feature of central and peripheral demyelinating disorders. Pain in multiple sclerosis tends to occur when the disease is well-established and usually lingers infinitely. Pain in Guillain-Barré syndrome tends to be particularly severe at the time of initial presentation and usually resolves over 8 to 12 weeks. Pain in both conditions is generally caused by either the direct effects of nerve injury or the result of paralysis and prolonged immobilization. Pain syndromes are well-defined in each disorder based on the underlying pathophysiology. Treatment involves a variety of pharmacologic and nonpharmacologic approaches individualized for each specific pain syndrome.