Current advances in immunology have led to the identification of a population of novel innate immune T cells, called mucosa-associated invariant T (MAIT) cells. The cells in humans express an invariant TCRα chain (Vα7.2-Jα33) paired with a limited subset of TCRβ chains (Vβ2, 13 and 22), are restricted by the MHC class I (MH1)-related (MR)-1, and recognize molecules that are produced in the bacterial riboflavin (vitamin B2) biosynthetic pathway. They are present in the circulation, liver and at various mucosal sites (i.e. intestine, lungs and female reproductive tract, etc.). They kill host cells infected with bacteria and yeast, and secrete soluble mediators such as TNF-α, IFN-γ, IL-17, etc. The cells regulate immune responses and inflammation associated with a wide spectrum of acute and chronic diseases in humans. Since their discovery in 1993, significant advances have been made in understanding biology of MAIT cells and the potential role of these cells in the pathogenesis of autoimmune, inflammatory and infectious diseases as well as cancer in humans. The purpose of this review is to provide a current state of our knowledge about MAIT cell biology and delineate their role in autoimmune and inflammatory diseases (sterile or caused by infectious agents) and cancer in humans. A better understanding of the role of MAIT cells in human diseases may lead to novel ways of immunotherapies.