Since first reported in Europe in the early 1980s, extended-spectrum beta-lactamases (ESBLs) have spread worldwide. When producing these broad-spectrum plasmid-encoded enzymes, organisms become highly effective at inactivating penicillins, most cephalosporins, and aztreonam. Mainly produced by Klebsiella spp, ESBLs have been isolated worldwide in different species, most of them belonging to the Enterobacteriaceae. ESBL-producing bacteria can appear as in vitro susceptible to beta-lactams by conventional laboratory methods, making the laboratory diagnosis problematic. Once detected, all beta-lactams except carbapenem and beta-lactamase inhibitor compounds should be reported as resistant. In addition, organisms harboring ESBLs are frequently resistant to other antibiotic classes, such as fluoroquinolones and aminoglycosides. Because of the very limited remaining alternatives for treatment and ESBLs significant prevalence worldwide, infection control remains the best way to deal with this bacterial resistance mechanism.