Allergen specific immunotherapy (SIT) is the only treatment of IgE mediated allergies that is causative and has a long-term effect. Classically, SIT requires numerous subcutaneous injections of the allergen during 3-5 years. Over the last decade sublingual allergen applications have established as an alternative, but treatment duration could not be shortened. This review focuses on direct administration of vaccines in general and of allergens in particular into lymph nodes with the aim to enhance immunotherapy. Several studies have found that direct injection of antigens into lymph nodes enhanced immune responses. Recently we have focused on intralymphatic allergen administration in order to enhance SIT. Data in mouse models and in clinical trials showed that intralymphatic allergen administration strongly enhanced SIT, so that the number of allergen injections could be reduced to three, and the allergen dose could be reduced 10-100 fold. Intralymphatic injections proved easy, practically painless and safe. In mice and men, intralymphatic immunotherapy injecting allergens into a subcutaneous lymph node markedly enhances the protective immune response, so that both the dose and number of allergen injections can be reduced, making SIT safer and faster, which enhances patient convenience and compliance.