The use of synthetic peptide fragments of allergen molecules holds promise for the delivery of effective immunotherapy without IgE-mediated adverse events. Early studies were associated with frequent induction of allergic symptoms after treatment, mostly related to activation of allergen-specific effector T cells with high doses of peptides. More recently, low doses of peptides have been shown to modify clinical and laboratory surrogates without inducing adverse events. Studies are ongoing to define the optimal dose, dose interval, and route of administration. Current results indicate that treatment with peptides modulates the immune response by reducing T(H)2 responses to allergen and increasing IL-10 production and the activity of allergen-specific regulatory T cells. Further studies are required in larger numbers of subjects and with peptides derived from a variety of allergens.