Neuroinflammation is a characteristic of pathologically affected tissue in several neurodegenerative disorders. These changes can be observed in the brainstem and spinal cord of amyotrophic lateral sclerosis (ALS) cases and in mouse models of the disease. They include an accumulation of large numbers of activated microglia and astrocytes, as well as small numbers of T cells, mostly adhering to postcapillary venules. Accompanying biochemical alterations include the appearance of numerous molecules characteristic of free‐radical attack, the occurrence of proteins associated with activation of the complement cascade, and a sharp upregulation of the enzyme cyclooxygenase 2 (COX‐2). Anti‐inflammatory agents may have a role to play in treating ALS. COX‐2 is a particularly attractive target because of its marked increase in ALS spinal cord. © 2002 Wiley Periodicals, Inc. Muscle Nerve 26: 459–470, 2002