The intestinal tract provides an important reservoir for antibiotic-resistant gram-negative bacilli, including Enterobacteriaceae species, Pseudomonas aeruginosa, and Acinetobacter baumannii. Selective pressure exerted by antibiotics plays a crucial role in the emergence and dissemination of these pathogens. Many classes of antibiotics may promote intestinal colonization by health care-associated gram-negative bacilli, because the organisms are often multidrug resistant. Antibiotics may inhibit colonization by gram-negative pathogens that remain susceptible, but the benefits of this effect are often limited because of the emergence of resistance. Antibiotic formulary alterations and standard infection control measures have been effective in controlling outbreaks of colonization and infection with antibiotic-resistant gram-negative pathogens. Additional research is needed to clarify the role of strategies such as selective decontamination of the digestive tract and decontamination of environmental surfaces and of patients' skin and wounds.