The complement (C) system plays important roles in host defense but activation at inappropriate sites or to an excessive degree can cause host tissue damage. C has been implicated as a factor in the causation or propagation of tissue injury in numerous diseases. The brain is an immunologically isolated site, sheltered from circulating cells and proteins of the immune system; nevertheless, there is a growing body of evidence implicating C in numerous brain diseases. In this brief article we review the evidence suggesting a role for C in diseases of the central and peripheral nervous system and discuss the possible sources of C at these sites. Some brain cells synthesize C and also express specific receptors; some are exquisitely sensitive to the lytic effects of C. The evidence suggests that C synthesis and activation in the brain are important in immune defense at this site, but may also play a role in brain disease.