Although research on the role of single nutrients in immune function is extensive, this is not the case for multiple nutrients and subsequent nutrient-nutrient interactions. After presenting a brief overview of immune function, the authors consider reports that examine imbalance of more than one nutrient and interactive effects on immunocompetence. Availability of one nutrient may impair or enhance the action of another in the immune system, as reported for nutrients such as vitamin E and selenium, vitamin E and vitamin A, zinc and copper, and dietary fatty acids and vitamin A. Nutrient-nutrient interactions may negatively affect immune function. For example, excess calcium interferes with leukocyte function by displacing magnesium ions, thereby reducing cell adhesion. Because of consumer interest in supplementation to improve immune function, the potential for harm exists. Research is needed to improve knowledge in this area so that recommendations can be made with more confidence.