For many years, peptide supplementation often combined with other substances has been used to boost the immune system. However, the interaction between the peptide metabolism and the intestine barrier, the immune system, the nitrogen requirements and the lean body mass composition or the nitric oxide production have to be understood to make a more realistic approach of the utility of these peptides in the immune modulation. In addition, the organism is reacting to stress differently according to time. Therefore, many questions remain unsolved regarding the immune modulating diets: which are the patients that will benefit? When should the nutrients be delivered and at which dose? And mainly which are the effective nutrients? This review will design the relation between protein metabolism and immune system as well as intestinal barrier and nitrogen balance, and focus on the demonstrated effects of glutamine, arginine and ketoglutarate ornithyl.