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The present guideline on allergen-specific immunotherapy (SIT) was established by the German allergy societies in conjunction with other scientific and medical societies (dermatology, ear-nose-throat, pediatrics, lung and airway diseases) and a patient support group according to criteria of the Association of the Scientific Medical Societies in Germany (AWMF). Subcutaneous immunotherapy (SCIT) is a unique causal treatment of IgE-mediated allergic diseases and induces longterm tolerance to the applied allergens due to numerous immunologic effects. Non-modified allergens are used as aqueous or physically coupled (depot) allergen extracts, chemically modified allergens (allergoids) are used as depot extracts for SCIT. Efficacy of SCIT has been demonstrated for pollen and house dust mite allergens in a large number of studies in patients with allergic rhinoconjunctivitis, and for animal dander (cat) and mold allergens (Alternaria, Cladosporium) in few studies. SCIT has been well-studied in intermittent and mild persisting IgE-mediated allergic asthma and is recommended as a therapeutic option besides allergen avoidance and pharmacotherapy. Preventive aspects, particularly reduced development of bronchial asthma and less novel allergic sensitizations, are increasingly considered during the decision for SCIT. In case of systemic reactions due to Hymenoptera (bee, wasp) venom allergy SCIT has excellent efficacy and should be continued for at least 3 - 5 years. An extended, sometimes lifelong SCIT, is necessary in a few patients. SCIT is indicated in patients with IgE-mediated sensitizations and corresponding clinical symptoms to allergens which do not permit allergen avoidance and which are available as suitable extracts. Diagnostic procedures, indication and selection of appropriate allergens for SCIT are made by a physician with certified training or qualified knowledge and skills in allergology. Contraindications have to be considered on an individual basis. Injections of SCIT are administered by a physician experienced in this therapy and who is able to perform emergency treatment in case of an allergic adverse event. Patients information and documentation are mandatory previous to the start of SCIT. Children tolerate SCIT very well and benefit especially from its immuno-modulatory effects. Systemic adverse reactions can occur due to SCIT, being rare in case of complete adherence to safety standards. Most adverse events are mild to moderate and easily treatable. Risk factors for and sequels of unwanted systemic effects can effectively be minimized by training the staff members involved, adhering to safety standards and immediate emergency treatment. Sublingual immunotherapy (SLIT) is an option for adults with allergic rhinoconjunctivitis due to pollen allergens, particularly if SCIT is not suitable. In house dust mite allergy and allergic asthma, SLIT does not substitute SCIT. Due to the present data, SLIT is not recommended for routine use in children and adolescents. A final conclusion on SLIT for children and adolescents is warranted if further study results are available. Various research fields like allergen characterization, routes of application, adjuvants, updosing regimen and preventive aspects demonstrate new developments in SIT being currently examined for clinical efficacy.