Extended-spectrum beta-lactamases (ESBLs) are extremely broad spectrum beta-lactamase enzymes found in a variety of Enterobacteriaceae. Most strains producing these beta-lactamases are Klebsiella pneumoniae, other Klebsiella species (i.e., K. oxytoca), and Escherichia coli. When producing these enzymes, organisms become highly effective at inactivating various beta-lactam antibiotics. In addition, ESBL-producing bacteria are frequently resistant to many classes of antibiotics, resulting in difficult-to-treat infections. Other problems due to ESBL-producing bacteria are difficulty in detecting the presence of ESBLs, limited treatment options, and deleterious impact on clinical outcomes. Clinicians should be familiar with the clinical significance of these enzymes and potential strategies for dealing with this growing problem.