Aeromonads are environmental microorganisms that can be responsible for both human and animal infections. Individual Aeromonas strains can produce up to three different, inducible, chromosomally encoded beta-lactamases, including a group 1 molecular class C cephalosporinase, a group 2d molecular class D penicillinase, and a group 3 molecular class B metallo-beta-lactamase, which contribute to beta-lactam resistance in members of this genus. Among these enzymes, the metallo-beta-lactamases are clinically relevant because of their ability to hydrolyze carbapenem antibiotics, and also represent a relevant investigational model for studying molecular class B beta-lactamases because of their unique enzymological behavior. An overview on the distribution, genetics, and enzymology of these enzymes is reported, and the contribution of these enzymes to microbial drug resistance is also discussed.