Amyotrophic lateral sclerosis (ALS) is a lethal neurodegenerative disease in which motor neurons in the nervous system die. The cause is unknown, and no effective treatment exists. Mutations in the gene for superoxide dismutase found in a subpopulation have led to an animal model, but research with these mice has not produced complete insight into the disease mechanism. Studies with isolated motor neurons may produce important information. This review discusses approaches to culture motor neurons - single cells, cocultured with other cells, and in intact preparations, such as the spinal or cortical slice. Motor neurons in monoculture are suitable for acute but not for chronic studies, whereas cocultures and slices survive up to months and are used for chronic studies. Results with toxic substances believed to play a role in the disease, such as oxidants and glutamate, and of studies where the energy status of the cells is manipulated, are presented.