The T-cell component of the antigen-specific immune response is the target of various novel interventions to modify chronic immunologic disorders, such as allergic diseases. Recent clinical trials have evaluated the safety and efficacy of therapeutic vaccines consisting of short, synthetic, allergen-derived peptides, corresponding to T-cell epitopes from the eliciting antigen. The main advantage of such an approach is the reduction in systemic, immunoglobulin E-mediated adverse events compared with existing whole allergen immunotherapy, often referred to as ‘allergy shots’. T-cell peptide epitopes, although capable of inducing immunologic tolerance, are short linear structures that have reduced ability to cross-link mast cell- and basophil-bound immunoglobulin E. The precise mechanism of tolerance induction remains incompletely defined. However, recent data indicate that peptide therapy induces/expands a population of antigen-specific regulatory T-cells. A novel form of treatment combining efficacy with a substantially decreased occurrence of adverse events is likely to have a major impact on the management and prevalence of allergic diseases. Furthermore, the principles of epitope-specific therapy hold promise for the development of therapeutic vaccines for the treatment of autoimmune diseases.