Conjugated linoleic acid (CLA), isomers of linoleic acid (C18:2) have many biological effects, including potential immunomodulatory potential. CLA is an unrecognized nutrient that significantly protects lymphoidal and nonlymphoidal tissues from lymphoid events during immune stimulation. This protection is through the regulation of lipid eicosanoid mediators while nonlymphoidal tissues prevent their negative feedback on the immune response. With lipid mediator modulation there is enhanced immunity, improved efficiency of feed use, changes in body composition, and decrease in diseases with immune response. With regard to the immune system, it is not clear whether individual isomers of CLA could act similarly or differently. In this chapter, we are trying to uncover most of the fundamental findings to explore the effects of CLA in relation to immunomodulation.