Publisher Summary This chapter focuses on ADP-ribosylating toxins, which are a variety of bacterial proteins with totally unrelated structures that have in common only one feature: they contain an enzyme with ADP-ribosyltransferase activity. This growing family of enzymes shows that ADP-ribosylation is also an enzymatic reaction with an important role in the posttranslational modification of the eukaryotic cells. Based on their overall structure the toxins can be divided into A/B toxins, binary toxins, or A/only toxins. The A domain contains the enzymatic toxic activity, while the B domain is a non-toxic part that functions as a carrier or delivery system for the A domain. Two types of ADP-ribosylation reactions are known to occur in nature: poly- and mono-ADP-ribosylation. Since the target proteins of ADP-ribosylating toxins are all located in the cytosol or in the inner face of the cytoplasmic membrane, the toxins need to cross the cell membrane in order to reach their intracellular targets. The molecular, functional, and evolutionary aspects of ADP-ribosylating toxins have been discussed, along with different types of bacterial toxins.