Amyotrophic lateral sclerosis is a progressive neurodegenerative disorder of motor neurons and their axons characterized by signs of upper and lower motor neuron dysfunction. When clinical features are restricted to either upper or lower motor neurons, limited to one or two body regions, or associated with non-motor manifestations, it is important to consider atypical motor neuron disorders. These are a group of disorders with varied etiologies that resemble amyotrophic lateral sclerosis in many respects but may possess distinct clinical, pathologic, and laboratory features. Some of these disorders are potentially reversible or have a better prognosis than amyotrophic lateral sclerosis. Recognizing these disorders early is necessary in order to initiate specific treatments when available and appropriately counsel patients particularly in the setting of genetic disorders.