Bacterial pathogens utilize toxins to modify or kill host cells. The bacterial ADP-ribosyltransferases are a family of protein toxins that covalently transfer the ADP-ribose portion of NAD to host proteins. Each bacterial ADP-ribosyltransferase toxin modifies a specific host protein(s) that yields a unique pathology. These toxins possess the capacity to enter a host cell or to use a bacterial Type III apparatus for delivery into the host cell. Advances in our understanding of bacterial toxin action parallel the development of biophysical and structural biology as well as our understanding of the mammalian cell. Bacterial toxins have been utilized as vaccines, as tools to dissect host cell physiology, and more recently for the development of novel therapies to treat human disease.