This chapter provides a brief review of the literature on immunomodulation by aflatoxin and other mycotoxins, examines immunomodulation by mycotoxins that co-occur in food, reviews possible mechanisms through which mycotoxins exert their effects, and considers future research in the field. Studies conducted in several species of animals and in animal and human cell cultures have shown that aflatoxins act as immunomodulators, primarily as immunosuppressors, of various aspects of cell-mediated immunity and phagocytic cell function. The effect of aflatoxin on humoral immunity in animals is less consistent. Recently, two studies have been published that show association between aflatoxin B1 albumin adduct levels in blood and antibody and cellular immune status of humans chronically exposed to aflatoxin in their diet. Several other immunotoxic mycotoxins co-occur with aflatoxin in foods, and are likely to have an additive, if not synergistic, effect on the immune system. Aflatoxin seems to exert its immunomodulatory effects by modulating cytokine production either at the mRNA or protein level, but, the mechanisms of immune modulation by aflatoxin and other mycotoxins remain to be clearly determined. © CAB International 2008.