iNKT and MAIT cells are innate-like T cells sharing many characteristics. These include a restricted TCR repertoire, made of an invariant TCR-alpha chain, recognition of non-protein antigens presented by the nonpolymorphic class Ib molecules CD1d and MR1, and an effector memory phenotype. These innate-like T cells are conserved in mammals, and are abundant in blood and tissues such as the liver, mucosa and skin. These cells can respond rapidly through TCR activation and inflammatory cytokines thereby stimulating immune response against infectious pathogens as well as participating to tissue homeostasis. Studies in patients and mouse models have revealed their ambivalent roles, being either protective or deleterious in various autoimmune, metabolic and infectious diseases. Their activation and function in different pathological contexts will be presented and discussed.