Immunonutrition is the maintenance and induction of immune homeostasis with the use of nutritional factors, the so called, immunonutrients. Immunonutrition focuses on four “Is” representing an equal number of systemic responses with regards to: a) Immunity, b) Infection, c) Inflammation and d) Injury. Although at the early stages of the development of immunonutrition, its application was focused on malnourished patients, with a latter extension in the intensive care unit setting, today we acknowledge the great importance of immunonutrients in rheumatology. In rheumatic diseases (RDs), all the “Is” representing the four aims and targets of immunonutrition are fulfilled. Impaired Immunity is the hallmark of RDs, with both innate and adaptive immunity contributing to the development and course of each disease entity, representing distinct immunoregulation abnormalities, often paired with micronutrient deficiencies. Infections are both drivers and a frequent epiphenomenon of systemic RDs. Subclinical inflammation is propagated long before the first signs or symptoms of RDs and musculoskeletal conditions (injury) are apparent in all patients with RDs, accompanied by pain, underlying connective tissue disease and the consequent reduction in the function of musculoskeletal. Herein, the role of probiotics, curcumin, vitamins, Selenium, Zinc and n-3 fatty acids as immunonutrients is discussed.