Heterothallism is dependent upon the obligatory cross-mating between self-sterile homokaryotic individuals and represents a common pattern of sexuality in yeasts and molds. Heterothallic reproductive cycles have recently been discovered in three Aspergillus species of medical and economic importance, namely Aspergillus fumigatus,A. parasiticus and A. flavus. Together with Aspergillus udagawae (Neosartorya udagawae), heterothallism has now been discovered in a total of four aspergilli that affect human health or economy. These fungi appear to express relatively low levels of fertility compared to other heterothallic or homothallic aspergilli and require unusually fastidious environmental parameters to complete the sexual cycle. Because the purpose of sex is to reproduce, we favor the hypothesis that while fertility of these species is on the decline this is compensated by their proficiency to reproduce asexually in a wider range of environmental conditions. Heterothallism in these species could provide an invaluable tool for the recombinational analysis of factors relevant to pathogenicity or toxin production. There is concern, however, whether extensive recombinational analysis can be very practical in light of the fact that formation of ascospores in these species requires a long period of time and the construction of genetically marked strains is likely to decrease fertility even further.