As our knowledge of amyotrophic lateral sclerosis (ALS) increases, the salient question has become: Is ALS a single disease or a group of diseases with a final common pathway? Traditionally, ALS has been defined as a rapidly progressive neurodegenerative disorder that affects the large motor neurons of the brain and spinal cord. It presents with an upper or lower motor neuron pattern of weakness but progresses to include all motor neurons (upper and lower, bulbar, cervical, thoracic, and lumbar). Cognition was thought to be affected in only a small subset of patients with ALS. The primary causation theory was that ALS was the result of a single common exposure or genetic mutation, and the primary pathologic finding was simple motor neuron degeneration. Recent studies on the genetics of ALS have changed this view.