Fungi in general and, Aspergillus fumigatus (A. fumigatus) in particular, are able to produce complex patterns of IgE-binding molecules. Robotics-based high throughput screening of A. fumigatus cDNA libraries displayed on phage surfaces revealed at last 81 different sequences encoding structures potentially able to bind to serum IgE of sensitised individuals suffering from A. fumigatus-related complications. Although not all of these allergens have been characterised in detail, A. fumigatus still represents the best investigated allergenic source. A total of 23 A. fumigatus allergens are recorded by the official allergen list of the International Union of Immunological Societies (http://www.allergen.org) and this is by far the longest allergen list reported for a single allergenic source. The IgE-binding molecules include species-specific as well as phylogenetically highly conserved cross-reactive structures and such with unknown function. A subset of cDNAs have been used to produce and characterise the corresponding recombinant allergens which have proven to be useful diagnostic reagents allowing specific detection of A. fumigatus sensitisation and differential diagnosis of allergic bronchopulmonary aspergillosis. Structures highly conserved through different species like manganese-dependent superoxide dismutase, P2 acidic ribosomal protein, cyclophilins and thioredoxins induce, beyond sensitisation, IgE antibodies able to cross-react with the corresponding homologous self-antigens. The frequently observed cross-reactivity is traceable back to shared discontinuous B-cell epitopes as shown by detailed analyses of the crystal structures.