The prevalence of sensitization to molds is low in healthy people, but significant in asthmatics. As it has not yet been possible to establish a cause-and-effect relationship between the presence of mold allergens and the occurrence of allergic symptoms, there is a great deal of uncertainty. The update of the S2k guideline “Medical–clinical diagnostics for indoor mold exposure” should help to objectify the topic. Based on the recommendations listed there for the diagnosis of suspected IgE-mediated mold allergy, this article presents the possibilities of skin tests, IgE determinations, and other in vitro test options, but also their limitations in clarifying the cause. Potential possibilities include component-resolved allergy diagnostics, while the limitations include the difficult standardization of test allergen extracts due to the complex allergen source and the insufficient commercial availability of the test extracts. A diagnostic algorithm is presented as a tool for a systematic approach to patients with suspected mold-associated respiratory allergy.