© 2014 by Nova Science Publishers, Inc. All rights reserved. Aflatoxins are secondary metabolites produced by fungi of the Aspergillus species. They occur as contaminants in a variety of food and feed stuffs that have been infected with the producing fungi. Aflatoxin exposure is known to cause a number of acute and chronic effects in both humans and animals, including immunosuppression, liver and other cancers, and failure of vaccination regimens. The immunomodulatory effects of the aflatoxins have been shown to affect cell-mediated immunity more than humoral immunity. In particular, aflatoxin exposure modulates secretion of inflammatory cytokines and phagocytic function. Decreases in phagocytosis and inflammation observed following aflatoxin exposure may reduce the effectiveness of the host immune response to infection, thereby increasing susceptibility to infection in individuals exposed to these toxins. The aim of this chapter is to summarise the immunomodulatory effects of aflatoxin exposure in order to better understand its potential immunosuppressive effects in humans and animals. The relationship between these immunosuppressive actions and susceptibility to infection will also be discussed.