Various non-peptidic ligands which specifically activate most of circulating human Vgamma9/Vdelta2 T lymphocytes are now known. Most of these are so-called phosphoantigens and directly trigger the Vgamma9/Vdelta2 TCR expressing cells, without need for MHC-restricted presentation molecules. Although some potent phosphoantigens currently involved in clinical trials are chemically-synthesized molecules, most of the natural antigens were isolated from microbial cultures. The structures and biosynthesis of phosphoantigens are reviewed here and the possible physiological significance of their recognition by gammadelta T lymphocytes is discussed.