Multiple sclerosis (MS) is the most frequent demyelinating disease of the central nervous system, with versatile manifestations--relapsing-remitting or progressive--and an unpredictable course, with prognoses ranging from minimal neurological impairment to severely disabled. Disease modifying agents can minimize relapse rate and slow disease progression. Yet most patients suffer relapses and progression despite use of these agents. Several of the manifestations of MS may cause overall decrease in the performance of the aviator. These include cognitive impairment, fatigue, and depression. Episodes of spasms, dysarthria, ataxia, parasthesias, diplopia, and hemiplegia, as well as drug side effects may also affect flight. Seizures and episodes of vertigo may occur suddenly and result in in-flight incapacitation. We present our experience with two aviators with definite MS and a navigator with probable MS. The various manifestations of MS are specifically addressed with an emphasis on the aeromedical implications.