Amyotrophic Lateral Sclerosis (ALS), also known as Motor Neuron Disease (MND) or Lou Gehrig's Disease, is a neurodegenerative disease that results in the progressive loss of motor neurons that control voluntary muscles. ALS is the most common form of the motor neuron diseases. Early symptoms of ALS include stiff muscles, muscle twitches, and gradual increasing weakness and muscle wasting. Limb-onset ALS begins with weakness in the arms or legs, while bulbar-onset ALS begins with difficulty speaking or swallowing. Around half of people with ALS develop at least mild difficulties with thinking and behavior, and about 15% develop frontotemporal dementia. Motor neuron loss continues until the ability to eat, speak, move, and finally the ability to breathe is lost with the cause of early death usually being respiratory failure.

Most cases of ALS (about 90% to 95%) have no known cause, and are known as sporadic ALS. However, both genetic and environmental factors are believed to be involved. The remaining 5% to 10% of cases have a genetic cause linked to a history of the disease in the family, and these are known as familial ALS. About half of these genetic cases are due to one of two specific genes. The diagnosis is based on a person's signs and symptoms, with testing done to rule out other potential causes.

There is no known cure for ALS. The goal of treatment is to improve symptoms. Treatments that slow ALS include riluzole (extends life by two to three months) and sodium phenylbutyrate/ursodoxicoltaurine (extends life by around seven months). Non-invasive ventilation may result in both improved quality and length of life. Mechanical ventilation can prolong survival but does not stop disease progression. A feeding tube may help maintain weight and nutrition. Death is usually caused by respiratory failure. The disease can affect people of any age, but usually starts around the age of 60. The average survival from onset to death is two to four years, though this can vary, and about 10% survive longer than ten years.

Descriptions of the disease date back to at least 1824 by Charles Bell. In 1869, the connection between the symptoms and the underlying neurological problems was first described by French neurologist Jean-Martin Charcot, who in 1874 began using the term amyotrophic lateral sclerosis.