Type 1 diabetes mellitus is caused by the T cell mediated autoimmune destruction of insulin-producing beta cells of the islets of Langerhans within the pancreas. Current immunotherapy strategies are aimed at directly inactivating the autoreactive T cells and/or inducing T cells with regulatory capabilities. At the preclinical level, several strategies that employ TCR antagonists -- including monoclonal antibodies, autoantigen-specific peptides and soluble TCR ligands -- are showing promise and being developed for clinical application. Several of these approaches employing monoclonal antibodies against the TCR-CD3 complex or soluble peptide antigens are producing favorable results in the clinic.