Aspergillus fumigatus can be regarded as the most important airborne fungal pathogen of patients under continuous immunosuppression. Recognition, phagocytosis and consecutive killing of conidia and hyphae by phagocytes contribute to the fungal clearance as well as to the generation of a proinflammatory immune response to trigger local infiltration of neutrophils and their migration to the site of infection. However, A. fumigatus has an arsenal of weapons protecting the fungus from the residual immune system in immunosuppressed patients. The ‘street smart’ attributes of A. fumigatus include the rodlet layer composed of the hydrophobin RodA covering the surface of conidia. In addition, A. fumigatus has some features allowing the fungus to interfere specifically with the immune response. Recent data of our laboratory showed that dihydroxy naphthalene (DHN) melanin is essential not only for inhibition of apoptosis of phagocytes by interfering with the host PI3K/Akt signaling cascade but also for effective inhibition of acidification of conidia-containing phagolysosomes. Furthermore, other compounds like gliotoxin might contribute to virulence. Also, we have carried out a number of proteomic and transcriptomic studies aiming at the characterisation of host pathogen interactions but also at the identification of antigens both for diagnosis and vaccination.