Cadmium (Cd) is an underground mineral widely used in the steel industry, in plastics, and as a component of batteries. It is an industrial and environmental pollutant released as an air contaminant from fertilizers and, more prominently, in the form of wastewater. Food, drinking water, and, mainly, inhalation of smoke from cigarettes are sources of daily exposure of humans to the heavy metal. Although Cd has no known useful function for humans as well as other organisms, it appears to evoke in cells a number of responses that involve not only death signaling but also protective reactions against the toxicity. This finding prompted a number of experimental studies aimed to elucidate the cellular and molecular aspects of Cd-dependent regulation of gene expression and signal transduction pathways in different model system. Here, the authors briefly review the role of Cd as a transcriptional regulator in diverse cytotypes of human origin, focusing in particular on its effects on two classes of genes, i.e., stress-response genes such as metallothioneins (MTs), heme oxygenase, and heat shock proteins (hsps), and apoptosis-related genes, but giving also an overview of many other examples of genes involved in cell metabolism and both intracellular and extracellular signalization whose expression levels are controlled by Cd.