Immunotoxicology is the study of drugs and chemicals that produce adverse effects on the immune system. Adverse immune effects include suppression, leading to compromised ability to fight infections, or enhancement, which could be involved in hypersensitivity (allergy) or autoimmunity. It has been appreciated for hundreds of years that diseases are associated with various occupations, such as respiratory diseases in those working with grains, coal, metals, or animals. We now understand that many of these occupational diseases are the result of an unregulated immune response to a specific agent. Similarly, occupational exposures to various chemicals can produce dermatitis, again due in part to unregulated immune responses in the skin. Additionally, occupational chemical exposures have been demonstrated to induce immune suppression. This chapter provides an overview of the immune system, a synopsis of standard assays to evaluate immunotoxic potential of occupational chemicals, and descriptions of effects of several occupational immunotoxicants with a focus on human exposures and doses. Consideration is given to current data gaps and potential use of novel technologies to more precisely define effects and mechanisms of occupational immunotoxicants.