When muscular atrophy develops in multiple sclerosis (MS) patients, its etiology may vary from benign to serious. We describe an individual with a 24-year history of MS who developed amyotrophic lateral sclerosis (ALS). The literature is reviewed with particular attention to the clinical and electrophysiologic characteristics of patients with MS and muscular atrophy and to those rare patients with concurrent MS and ALS. Circumstances warranting a heightened suspicion for concurrent ALS are discussed and careful evaluation of similar patients is encouraged.