In spite of extensive research, amyotrophic lateral sclerosis (ALS) remains an enigmatic and incurable disease. Based on the different hypothetical pathogenetic mechanisms, several rational strategies have been considered with the aim of slowing the progression of neuronal loss associated with the disease. These strategies have included the use of glutamate antagonists, antioxidants, immunosuppressants and neurotrophic factors.Although no specific therapy is yet available for ALS, symptomatic pharmacological treatment certainly has a place in the management of this disorder. Anticholinergic drugs may be tried against sialorrhoea, and benzodiazepine derivatives and baclofen against muscle cramps and spasticity. Anxiety and insomnia are usually relieved by low doses of benzodiazepine derivatives or, in later stages, by morphine. Nonpharmacological treatment and support are also very important.