Since the discovery of immunoglobulin E (IgE) as a mediator of allergic diseases in 1967, our knowledge about the immunological mechanisms of IgE‐mediated allergies has remarkably increased. In addition to understanding the immune response and clinical symptoms, allergy diagnosis and management depend strongly on the precise identification of the elicitors of the IgE‐mediated allergic reaction. In the past four decades, innovations in bioscience and technology have facilitated the identification and production of well‐defined, highly pure molecules for component‐resolved diagnosis (CRD), allowing a personalized diagnosis and management of the allergic disease for individual patients. The first edition of the “EAACI Molecular Allergology User's Guide” (MAUG) in 2016 rapidly became a key reference for clinicians, scientists, and interested readers with a background in allergology, immunology, biology, and medicine. Nevertheless, the field of molecular allergology is moving fast, and after 6 years, a new EAACI Taskforce was established to provide an updated document. The Molecular Allergology User's Guide 2.0 summarizes state‐of‐the‐art information on allergen molecules, their clinical relevance, and their application in diagnostic algorithms for clinical practice. It is designed for both, clinicians and scientists, guiding health care professionals through the overwhelming list of different allergen molecules available for testing. Further, it provides diagnostic algorithms on the clinical relevance of allergenic molecules and gives an overview of their biology, the basic mechanisms of test formats, and the application of tests to measure allergen exposure.

The prediction of allergen cross-reactivity is currently largely based on linear sequence data, but will soon include 3D information on homology among surface exposed residues. To evaluate procedures for these predictions, we need ways to quantitatively assess actual cross-reactivity between two allergens. Three parameters are mentioned: 1) the fraction of the epitopes that is cross-reactive; 2) the fraction of IgE that is cross-reactive; 3) the relative affinity of the interaction between IgE and the two allergens. This editorial briefly compares direct binding protocols with the often more appropriate reciprocal inhibition protocols. The latter type of protocol provides information on symmetric versus asymmetric cross-reactivity, and thus on the distinction between complete (= sensitising) allergens versus incomplete, cross-reacting allergens. The need to define the affinity threshold of the assay and a caveat on the use of serum pools are also discussed.