Dr. Culebras of Upstate Medical University, SUNY, in Syracuse, NY, reviews sleep-related manifestations in patients with multiple sclerosis and points out the intimate relationship between this condition, fatigue, and excessive daytime sleepiness. Several cases of symptomatic narcolepsy have been described in patients with multiple sclerosis raising the question of demyelinating plaques involving hypothalamic centers. Other studies have indicated that disruption of nocturnal sleep as well as circadian rhythm disorders may underlie fatigue responsive to sleep management. Case studies have described REM sleep behavior disorder in association with acute multiple sclerosis. There is growing evidence that sleep-related respiratory disturbance is common in patients with multiple sclerosis and that in general the condition is underdiagnosed. Sleep disorders are significant contributors to fatigue in multiple sclerosis, and this notion highlights the desirability of conducting an in-depth evaluation of sleep-related manifestations, which are commonly multifactorial in patients with multiple sclerosis.