Specific allergen immunotherapy has been widely practised for almost 100 years. Whilst this approach is disease-modifying and efficacious, the use of whole allergen preparations is associated with an unacceptably high prevalence of allergic adverse events during treatment. Many approaches to reduce the allergenicity of immunotherapy preparations whilst maintaining immunogenicity are under development. One such approach is the use of short synthetic peptides which represent major T-cell epitopes of the allergen. Major potential advantages of this approach include markedly reduced capacity to cross-link immunoglobulin-E and activate mast cells and basophils, and ease of manufacture and standardization. Promising results in preclinical studies have led to the translation of this approach to clinical studies in humans. Peptide immunotherapy is currently under development for allergic and autoimmune diseases.