The purpose of this study was to compare the efficacy and safety of subcutaneous, sublingual, oral specific immunotherapy in patients who suffer from allergic conditions to pollen from trees, grasses and weeds, house dust mites and Alternaria alternata spores. A literature search was performed separately for each type of allergen and each administration route of the drug. As a result, it was found that all administration routes were quite effective. However, each type of immunotherapy was most effective for certain allergens. Subcutaneous and sublingual immunotherapy have proven effective for aeroallergens such as pollen from grass, trees, weeds and house dust mites. Despite this, subcutaneous immunotherapy had a number of disadvantages in the form of the duration of treatment and a greater prevalence of side effects. Some authors suggest that for allergies to house dust mites, the most effective method of immunotherapy was the subcutaneous method of administration, compared with sublingual and nasal. Sublingual therapy was safe enough for all types of allergens under study, however, to achieve the same effect as the subcutaneous method of administration. In addition, oral immunotherapy has been shown to be effective for food allergies with obvious symptoms of gastrointestinal disorders. In addition, oral immunotherapy is the only approved treatment for allergies in the elderly, due to the low risk of side effects. The time-accelerated and dosage-enhanced immunotherapy was also effective and safe. These data prove the effectiveness and safety of each administration route of specific allergens for specific immunotherapy in patients suffering from allergic rhinitis, bronchial asthma and even atopic dermatitis.© 2025 John Wiley & Sons Ltd.