Subsets of human gammadelta T cells recognize tumor cell-expressed ligands that are not seen by the T-cell receptor of conventional alphabeta T cells. Vdelta1 T cells recognize MHC class I chain-related molecules A and B and UL-16-binding proteins expressed at variable levels on epithelial tumor cells and some leukemias and lymphomas. In addition, therapeutically used aminobisphosphonates and synthetic phosphoantigens activate Vdelta2 T cells, the dominant subset of gammadelta T cells in human peripheral blood that display strong cytotoxicity towards various epithelial tumors. Intentional activation of gammadelta T cells in vivo and/or adoptive cell therapy with in vitro expanded gammadelta T cells holds considerable promise as a novel immunotherapy in certain types of cancer.