The recent discovery that T cells recognize endogenous and foreign lipid and glycolipid molecules presented by CD1 proteins has brought a major contribution in the understanding of innate and adaptive immune response to certain harmless antigens and infectious pathogens. Among (glyco)lipid-reactive T cells, CD1d-restricted natural killer (NK) T cells represent a population of innate/memory lymphocytes that, upon stimulation, rapidly release important amounts of immunoregulatory cytokines that in turn can shape the acquired immune response in a Th1 or a Th2 direction. Here we review the general features of these cells as well as their diverse influence in various disease models. A particular emphasis will be placed on the role of NK T cells in the promotion of asthma, a typical Th2-related inflammatory disease. Moreover, recent studies suggest that NK T cells could also be important in the modulation of the host immune response during helminthic infections, generally associated with dominated Th2 responses. Our current understanding of the role and of the mode of NK T cell activation during the initial immunological events that lead to the promotion of Th2 responses will be discussed.