Extended-spectrum beta-lactamases, most commonly found in Klebsiella pneumoniae and Escherichia coli, have increased markedly in the past decade, particularly in the intensive care unit setting. The problem has been significant in the United States but is even more prevalent in parts of Latin America and Asia. These plasmid-mediated beta-lactamases confer resistance to broad-spectrum beta-lactam antibiotics, including third- and fourth-generation cephalosporins, aztreonam, and extended-spectrum penicillins. Other resistances, such as aminoglycoside resistance and trimethoprim/sulfamethoxazole resistance, are often cotransferred on the same plasmid. Fluoroquinolone resistance is often associated, resulting in an organism that is resistant to most of the usual antimicrobial options. Although carbapenems are currently considered the drugs of choice for these pathogens, widespread use of these agents may lead to other resistance problems. Due to limited therapeutic options, prevention and control measures are important. Traditional infection control measures, such as contact precautions, are recommended to prevent spread in intensive care units. In addition, because this type of antimicrobial resistance appears to be particularly influenced by antibiotic utilization, antibiotic control measures may also be a very important intervention in limiting the spread of extended-spectrum beta-lactamases.