Abstract: Carbapenem antibiotics are typically reserved for serious nosocomial infections. Several classes of β-lactamases have emerged that possess carbapenem-hydrolyzing activity. Class A KPC-type β-lactamases have recently emerged in Klebsiella pneumoniae isolates from the northeastern United States. Class D OXA-type β-lactamases are typically found in Acinetobacter baumannii and Pseudomonas aeruginosa isolates from southern Europe. Class B metallo-β-lactamases are also typically found in A. baumannii and P. aeruginosa; regions in the Far East and Europe have been especially affected by bacteria carrying these enzymes. Most nosocomial pathogens that possess a carbapenem-hydrolyzing β-lactamases are frequently resistant to other classes of antibiotics, including aminoglycosides and fluoroquinolones. For infections caused by these highly resistant Gram-negative pathogens, polymyxin antibiotics are often administered, although concerns remain regarding their efficacy and toxicity.