Allergen-specific immunotherapy (SIT) is an effective form of treatment for IgE-mediated type I allergy and represents the only curative approach. Presently SIT is performed with complex natural extracts that contain allergens (representing active pharmaceuticals ingredients, APIs) together with non-allergenic proteins and other macromolecules. These extracts are difficult to standardize and it is not possible to define each component quantitatively. In order to overcome such difficulties in standardization and batch-to-batch consistency, highly purified recombinant allergens (rallergens) and hypoallergenic variants may be considered as novel candidates for the production of high quality therapeutic preparations offering safer and more effective SIT. The availability of detailed information on the characteristics of r-allergens makes it possible to apply a variety of methods in order to ensure purity, identity, quantity, safety and potency compared to allergen extracts. Besides determination of potential process-related contaminants such as endotoxin and residual host-cell-protein a central consideration focuses on the investigation of the folding status, as pathologic IgE-binding is highly dependent on the conformation of the molecules. The primary structure on the other hand determines the therapeutic potential through the specific T cell epitopes and the ability to induce a curative reorientation of the T-cell response. Suitable methods for evaluation of the relevant properties include immunologic methods such as ELISA and Western blots together with robust chromatographic and electrophoretic techniques. Promising results from early clinical studies suggest that the use of rallergens for SIT will become a reality and therefore it is appropriate to consider how all aspects of the quality of these proteins might be evaluated.