A great deal is known about the structure, function and metabolic effects of enzymatic bacterial toxins such as the diphtheria, pertussis and cholera toxins. By comparison, our understanding of the pore-forming, cytolytic toxins, particularly those produced by Gram-negative bacterial pathogens, is far less complete. The genetics and biochemistry of a large, newly discovered family of calcium-dependent, pore-forming cytotoxins (RTX toxins) produced by different genera of the Enterobacteriaceae and Pasteurellaceae are discussed in this review. This toxin family is especially noteworthy because the individual toxins often exhibit different cell- and host-specificity. A brief review is also included of two ancestrally unrelated groups of calcium-independent, pore-forming toxins, the haemolysins produced by Proteus mirabilis and Serratia marcescens and the aerolysins secreted by species of Aeromonas. Their structure and function are contrasted with those of the RTX family members. Emerging questions about the role of cytolysins in pathogenesis are presented. Perhaps the most important issue raised is whether or not less attention should be paid to the lytic capacity of these cytotoxins, with more energy being devoted to the understanding of their non-lytic inhibitory activities against host cells.