IgE antibodies play a key role in type I allergic reactions. Today, different in vitro immunoassays for allergen-specific IgE antibodies are available. However, some major issues should be taken into account for correct interpretation of specific IgE (sIgE) antibody results, as these assays do not demonstrate absolute positive and negative predictive values. Therefore, additional diagnostic tests are needed to make the correct diagnosis. During the last two decades significant progress in biochemistry and molecular biology enabled the detection and quantification of sIgE antibodies to allergen protein components and epitope-emulating peptides, also called molecular allergy diagnosis or component resolved diagnosis (CRD). In contrast to conventional sIgE antibody assays, molecular allergy diagnosis makes it possible to discriminate between genuine allergy and merely sensitisation, to establish personalized sensitization patterns and to assess the individual risk of severity of an allergic reaction and finally it helps us to predict the natural course. In this review the use of CRD in inhalant, food, latex and hymenoptera venom allergy will be discussed. The primary focus will be on the most relevant clinical applications of CRD rather than to describe all the currently available allergen components and epitopes. Appropriate experience of our own research group is provided.