In the last two decades, it has become clear that γδ T cells recognize a diverse array of antigens including self and foreign, large and small, and peptidic and non-peptidic molecules. In this respect, γδ antigens as a whole resemble more the antigens recognized by antibodies than those recognized by αβ T cells. Because of this antigenic diversity, no single mechanism-such as the major histocompatibility complex (MHC) restriction of αβ T cells-is likely to provide a basis for all observed T-cell antigen receptor (TCR)-dependent γδ T-cell responses. Furthermore, available evidence suggests that many individual γδ T cells are poly-specific, probably using different modes of ligand recognition in their responses to unrelated antigens. While posing a unique challenge in the maintenance of self-tolerance, this broad reactivity pattern might enable multiple overlapping uses of γδ T-cell populations, and thus generate a more efficient immune response.