In vitro studies of the use of immune cells and animal models demonstrate that conjugated linoleic acid (CLA), a lipid, modulates immune function. In addition, recent publications demonstrate that 2 active CLA isomers (ie, cis-9,trans-11 CLA and trans-10,cis-12 CLA) modulate immune function in humans. Aspects of both the innate and adaptive immune responses are affected by dietary CLA supplementation. CLA consists of a mixture of isomers, which reduced immune-induced wasting and enhanced ex vivo lymphocyte proliferation in broilers and decreased tumor necrosis factor alpha (TNF-alpha) and interleukin 6 (IL-6) production in rat models. In mice, ex vivo lymphocyte proliferation and IL-2 production were increased. Furthermore, evidence suggests that the cis-9,trans-11 and trans-10,cis-12 CLA isomers exert distinct effects on immune function. Specifically, these 2 isomers have differential effects on specific T cell populations and immunoglobulin subclasses in animal and human studies. Herein, a systematic review of the literature and relevant new data are presented with an aim to compare data and to present an overview covering the innate and adaptive components of the immune response that are regulated by CLA. In addition, potential mechanisms of action are discussed and the need for future studies on the immunomodulatory properties of CLA are outlined in detail. The understanding of the mechanism(s) by which CLA increases immune function will aid in the development of nutritionally based therapeutic applications to augment host resistance against infectious diseases and to treat immune imbalances, which result in inflammatory disorders, allergic reactions, or both.