The Serratia marcescens hemolysin represents the prototype of a growing family of pore forming toxins. The available bacterial genome sequences reveal Serratia hemolysin homologues in additional species. However, only S. marcescens hemolysin has been studied in great molecular detail. This family of toxins has nothing in common with the pore forming toxins of E. coli type (RTX toxins), the Staphylococcus aureus α-toxin or the thiol activated toxin of group A β-hemolytic streptococci (Streptolysin O). Studies on erythrocytes, eukaryotic cells and artificial black lipid membranes, have shown that the mechanism of pore formation of ShlA is different form other pore forming toxins. The S. marcescens hemolysin proteins ShlB and ShlA, exhibit protein sequence homologues in Proteus mirabilis, Haemophilus ducreyi, Yersinia pestis, Yersinia enterocolitica, Edwardsiella tarda, Photorhabdus luminescens and Xylella fastidiosa . The family of Serratia type pore forming toxins show a unique secretory mechanism which has been described as a two partner secretion system (TPSS) or type V-secretion system. Not only Serratia type pore forming toxins are secreted via TPSS but also adhesins from Bordetella pertussis, Erwinia chrysanthemi and Haemophilus influenzae. The uniqueness of the Serratia family is underlined by the fact that activation of ShlA by ShlB strictly requires phosphatidylethanolamine as a cofactor. And, quite unusual, ShlA undergoes a conformational change during activation. ShlA pore formation in erythrocytes and in nucleated eukaryotic cells results in cell lysis. In sub-lytic doses, as will normally be the situation in vivo, ShlA exerts additionally effects like vacuolization, cytoskeleton rearrangements and apoptosis. The knowledge of the structure, activation, secretion and mode of action of S. marcescens hemolysin has implications for proteins, related in sequence or in mode of secretion and activation.