In the last few decades, the importance of a functioning immune system and health status has become more evident. Multiple factors are able to influence the development of chronic diseases and diet is one of the most important environmental factors. Evidence demonstrates that dietary patterns high in fat and low in fiber are associated with the development of non-communicable diseases. Moreover, optimal nutritional status can modulate immune maturation and response to inflammation. During inflammatory conditions, nutritional deficiencies may occur, establishing a vicious circle, consequently a balanced nutritional status is essential to prevent and counteract infections. Dietary diversity can prevent allergic diseases and nutrients such as DHA, arginine, vitamins and trace elements have an impact on physical barriers (such as gut mucosal barrier and skin), on the immune system response and on microbiome modulation. Protein deficiencies can compromise innate and adaptive immune functions; arginine availability can affect the immune response in injured states and other disease processes; EPA and DHA can modulate both innate and adaptive immunity; prebiotics have a beneficial effect on the functioning of the immune system. Zinc, copper, selenium and iron are involved in the correct development and function of the immune system. Vitamins D, E, A, B and C have a role on immune system through different mechanisms of action. Since a complex interplay exists between diet, microbiome and epigenetic factors which determine nutrient-induced changes on the immune function, the effect of each single nutrient may be difficult to study. Well-designed intervention studies, investigating the effects of whole dietary pattern, should be performed to clarify impact of foods on the immune function and disease risk.