Aspergillus section Flavi includes aflatoxin-producing and nonproducing fungi. Aspergillus sojae is unable to produce aflatoxins and is generally recognized as safe for food fermentation. However, because of its taxonomical relatedness to aflatoxin-producing Aspergillus parasiticus and A. flavus, it is necessary to decipher the underlying mechanisms for its inability to produce aflatoxins. This review addresses the relationship between A. sojae and A. parasiticus and the advances that have been made in aflatoxin biosynthesis research, especially with regard to gene structure, genome organization, and gene regulation in A. parasiticus and A. flavus and how this has been used to assure the safety of A. sojae as an organism for food fermentation. The lack of aflatoxin-producing ability of A. sojae results primarily from an early termination point mutation in the pathway-specific aflR regulatory gene, which causes the truncation of the transcriptional activation domain of AflR and the abolishment of interaction between AflR and the AflJ co-activator. Both are required for gene expression. In addition, a defect in the polyketide synthase gene also contributes to its nonaflatoxigenicity.