Cd2+ pollution represents a serious global environmental risk. Understanding how microbes survive cadmium stress can facilitate the development of techniques to clean our environment and to prevent accumulation of this toxic heavy metal in the food chain. Genome-wide transcriptional changes induced by CdCl2 were determined and evaluated in Aspergillus nidulans. In addition to the reference strain, a ?atfA gene deletion mutant was also investigated to collect data on the regulatory role of AtfA transcription factor in this model organism. Up-regulation of the crpA Cu2+/Cd2+ pump and AN7729 putative bis(glutathionato)-cadmium transporter genes as well as transcriptional changes aiming to increase intracellular Cys availability were important parts of the efficient adaptation in both strains. Although deletion of atfA did not alter the cadmium tolerance of the fungus, the cadmium stress response of the mutant substantially differed from that of the reference strain. Promoter and transcriptional analyses of the “Two component signal transduction system” genes suggest that the AtfA-dependent regulation of these genes can be relevant in this phenomenon. We concluded that the regulatory network of A. nidulans has a high flexibility allowing the fungus to adapt efficiently to stress both in the presence and absence of this important transcription factor. Overall design: two strains (TNJ92 atfA gene deletion mutant and THS30 reference strain) were examined under two conditions (CdCl2 treated and untreated cultures) with three biological replicates (altogether 12 samples)