Allergen immunotherapy (AIT) represents the only way to modify the natural history of allergic diseases. Unfortunately, AIT is not always followed by a reduction in symptoms. The main reasons for such failure can be inadequate diagnosis and/or the poor treatment. In both cases, an incomplete or insufficient understanding of the component(s) responsible for the IgE sensitization on the one hand, and, on the other hand, the lack of a steady and reliable allergen mixture to be used for the desensitization process, could explain unsuccessful treatment. A more comprehensive IgE reactivity profile evaluation of the patient can be achieved by means of a molecule-based diagnostic approach, in order to distinguish genuine from panallergen-driven antigen recognition. At the same time, a better delineation of AIT products by means of molecular dissection, can allow a stronger correlation between diagnostic findings and immunotherapeutic intervention, thus facilitating the right prescription to the right patient.