Metal toxicants which affect the immune system may contribute to an increased incidence of autoimmune diseases, infectious diseases and cancer. In the recent past, there has been a growing concern among health and environmental scientists on the impact of environmental exposure to heavy metal lead on human health. In some instances the immune system appears to be exquisitely sensitive to the toxic heavy metal lead as compared to other toxicological parameters. Susceptibility to autoimmunity is determined by both heritable traits and environmental factors, and in this context there has been considerable interest in the influences that exposure to heavy metals may have on the initiation and/or progression of autoimmune diseases. This review discussed the immunomodulatory role of toxic heavy metal lead, on autoimmunity, phenotypic expression of the immune cells and hypersensitivity.