Cobalt (Co) is present in trace amounts in the environment but it can be toxic when it accumulates in cells. The question of how Co produces its toxic effects and how living organisms protect themselves from, and resist to, such a stress remains to be clarified. Studies pertaining to these issues were recently carried out in Escherichia coli and Salmonella enterica. Iron-sulfur proteins were identified as primary targets of Co ions. Perturbation of iron homeostasis, oxidative stress and possible effects on sulfur assimilation were noticed. Cells were found to respond by up-regulating genes involved in the biosynthesis of Fe-S clusters as well as genes involved in Co efflux. These data are summarized in this review article to provide a preliminary general view of Co toxicity mechanisms in these two bacterial models.