Amyotrophic lateral sclerosis (ALS), once thought to be a rare neurodegenerative disease, affects between 1.2 and 1.8/100,000 individuals. This age-dependent disorder, similar to other major neurological disorders of the aging population (Alzheimer's and Parkinson's disease) is increasing in incidence at a rate which cannot be accounted for by population aging alone. Multiple clinical variants of ALS are now recognized which are associated with a spectrum of clinical outcomes from aggressive to rather indolent. Three variants of ALS are generally accepted, including the western Pacific type (often associated with dementia), familial (the majority of which are autosomal dominant in their inheritance) and classic sporadic ALS. Considerable biological heterogeneity underlies the disease process of ALS. By the time ALS is clinically evident, derangements at the cellular level in ALS are extensive and include alterations in the cytoskeleton, mitochondrial function, microglial activation, and the metabolism of reactive oxygenating species and glutamate. Our understanding of the genetic aspects of the disease continues to expand. These observations have led to the suggestion that multiple distinct etiologies may be responsible. Recent advances have also included the observation that cognitive decline may be present in a population of patients not previously recognised. Significant advances in both symptomatic and adjunctive therapy have resulted in prolonged quality and duration of life.