The unique nature of Aspergillus fungi represents a challenge for scrutinizing the attributes that render these saprophytic microorganisms pathogenic or allergenic under certain environmental circumstances. Recent publication of the genomic sequence from an isolate of the major pathogen Aspergillus fumigatus denotes enormous progress in aiming at cellular features and gene products that contribute to its pathogenicity. Latest developments to study virulence-related characteristics comprise profiling techniques, conditional gene inactivation and precise manipulation of the genome by means of gene targeting. Advances in assessing the virulence potential of particular mutant strains in alternative test systems complement these approaches.