Infections with mold pathogens have emerged as an increasing risk faced by patients under sustained immunosuppression. Species of the Aspergillus family account for most of these infections, and in particular Aspergillus fumigatus may be regarded as the most important airborne pathogenic fungus. The improvement in transplant medicine and the therapy of hematological malignancies is often complicated by the threat of invasive aspergillosis. Specific diagnostic methods are still limited as are the possibilities of therapeutic intervention, leading to the disappointing fact that invasive aspergillosis is still associated with a high mortality rate that ranges from 30% to 90%. In recent years considerable progress has been made in understanding the genetics of A. fumigatus, and molecular techniques for the manipulation of the fungus have been developed. Molecular genetics offers not only approaches for the detailed characterization of gene products that appear to be key components of the infection process but also selection strategies that combine classical genetics and molecular biology to identify virulence determinants of A. fumigatus. Moreover, these methods have a major impact on the development of novel strategies leading to the identification of antimycotic drugs. This review summarizes the current knowledge on the biology, molecular genetics, and genomics of A. fumigatus.