Unbalanced nutrition with too much sugar, salt, and fat; a sedentary lifestyle; and the effects of a stressful obesogenic environment can compromise the host immune responses, increasing susceptibility to a wide range of age-related chronic diseases. The new field of nutritional immunology or immunonutrition primarily focuses on the role of diet and its nutritional contents in disease prevention, while there is extensive scientific evidence for the effects of malnutrition on immune function, going back more than 60 years. In fact, the system that classically fails in advanced protein–energy malnutrition (PEM) is the immune system. Deficiencies of vitamins and minerals can also lead to immune compromise, and some effects of classic vitamins, such as vitamin D, impact the immune system, as well as bone mineral metabolism. One of the assessments used since the early 1970s in clinical research on enteral and parenteral nutrition was delayed hypersensitivity to tuberculin, mumps, and streptokinase and streptodornase (SKSD) antigens. More recently, the interactions of obesity and immune function have been recognized.