Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease characterized by loss of upper and/or lower motor neurons. The clinical correlates of UMN disease include spasticity, pseudobulbar effect, hyperreflexia, and pathologic reflexes. LMN disease manifests as weakness, atrophy, fasciculations, cramps, and hyporeflexia. Affected individuals typically present with either asymmetric weakness and muscle atrophy of the extremities or with bulbar symptoms. The disease generally progresses rapidly, and gradually all muscles under voluntary control are affected. The worldwide annual incidence of ALS is about 1.8 per 100,000 population. ALS is sporadic in 90% of cases, whereas only 10% is familial. The mean age at onset of sporadic ALS is 65 years and a few years earlier for familial ALS. The cause of ALS is unknown. Mutations in the SOD1 gene account for 20% of familial and 5% of sporadic ALS. However, the precise mechanism by which mutant SOD1 leads to motor neuron degeneration has not been defined with certainty. Other possible causes include higher than normal levels of glutamate, impairment of the immune system, toxic metal poisoning, and smoking. The diagnosis of ALS is based on the clinical features and exclusion of conditions that can mimic ALS. Even though ALS is a fatal disease, with an average survival of 3 years from onset, adequate therapy and early palliative care can improve quality of life and prolong life in ALS patients.