Metallo-beta-lactamases have recently become more prominent among the beta-lactam-hydrolyzing enzymes. Two major functional groups of enzymes have been identified, with little structural similarity among the groups. One group is a set of enzymes with broad substrate specificities capable of hydrolyzing most beta-lactams except monobactams. A second group is composed of the "true" carbapenemases, enzymes that exhibit poor hydrolysis of penicillins and cephalosporins. This latter group has been found primarily in Aeromonas species. To date, only a small number of carbapenem-resistant isolates have been reported to produce metallo-beta-lactamases, in part because of the ease with which this resistance can be acquired by other means: permeability changes and an increase in chromosomal cephalosporinase production. However, the appearance of these enzymes on plasmids in Japan poses a worrisome problem. It is anticipated that plasmid-mediated resistance to carbapenems will continue to increase, perhaps compromising the use of these agents.