Autoimmune T cells reactive to beta-cell autoantigens are generally believed to play an essential role in the immune-mediated selective pancreatic islet beta-cell destruction process leading to insulin-dependent diabetes mellitus (IDDM). Many of the supportive data have been obtained from animal models of this disease, but often these data remain to be validated in human IDDM, including the nature of the responsible autoreactive T cells and their targets on the beta cells. In the last few years, however, considerable progress has been made, and several candidate autoantigens have been identified. Diabetogenic T-cell clones have been isolated and characterized in animal models, but for the majority of these clones, the target autoantigen is unknown. In humans, the first islet autoantigens recognized by autoreactive T cells have been defined. This opens the way to designing immunointerventive strategies selective for these T cells and their candidate target antigens, in an attempt to prevent the onset of IDDM. In this review, we described the significance of T lymphocytes for the pathogenic process leading to type 1 diabetes and our studies showing (auto)immune responses by beta-cell-reactive T lymphocytes of newly diagnosed patients.