During the last few years, our knowledge about the activation and control of non-major histocompatibility complex (MHC)-restricted innate effector lymphocytes (such as natural killer (NK) cells, NK T cells and gammadelta T cells) has advanced enormously and immunotherapeutic strategies based on these cell types receive more and more attention. Apart from NK cells, several lines of evidence indicate that T cells, which express an alternative T cell receptor (TCR) composed of a CD3-associated gammadelta heterodimer, also contribute to the innate immune defense against tumors. Human gammadelta T cells represent a small subset of T cells (1-10% of peripheral blood T cells) and differ from conventional MHC-restricted ass T cells in recognition of a unique set of antigens ("phosphoantigens") and the lack of requirement of classical antigen-presenting molecules. Besides their role in the innate immune response against pathogens based on the recognition of distinctive microbial metabolic products (metabolites of the non-mevalonate pathway of isoprenoid synthesis), Vgamma9Vdelta2 T cells that constitute the dominant fraction of gammadelta T cells in humans exert potent cytotoxic activity, especially against lymphoid malignancies, mediated by as yet only partially determined pathway(s) of tumor recognition. This article will review available evidence from pre-clinical and early clinical studies regarding the contribution of gammadelta T cells in the defense against lymphoid malignancies and highlights some important issues that need to be addressed in the future.