Immunocompetence refers to the capability of the host to launch an immune response against an infection of sufficient specificity and magnitude. It includes a highly sophisticated and dynamic network of mechanisms of both immune resistance (preventing pathogens from invading or eliminating the pathogens when they do invade) and tolerance (limiting the damage that is caused by the infection). Genetic strategies aiming at improving overall immunocompetence have the potential to reduce both the incidence and severity of infectious diseases, with resulting benefits of improved animal health and welfare and reduced reliance on antibiotics. To evaluate immunocompetence, direct strategies target animal resistance/tolerance to specific pathogens. However, these strategies may result in increased susceptibility to other diseases. An indirect and putatively global approach focuses on immune traits that would predict the responses to pathogens in general. In this approach, immunity traits such as blood cell composition, natural antibodies or vaccine responses may be considered as biologically relevant parameters to measure. We and others have already reported in different species, including pig and poultry, that immunocompetence traits are genetically determined by many genes that affect different components of the immune system. To assess whether they can be exploited in breeding programs there is a need to understand which parameters – genetics or environmental – characterize a healthy immune system and its natural variability. On the other hand, phenotypic and genetic relationships between immunocompetence and other traits of importance like performance, stress, welfare and health must be assessed, in light of the allocation theory, as investing more resources into one functional area may be detrimental to other ones. The presentation will provide a global overview of projects conducted in GABI GeMS team to understand whether exploiting the natural variability of immune traits for genetically enhancing animal global immunocompetence could be a promising approach to promote sustainable production.