The close relationship between colonization and the development of nosocomial infections has been demonstrated. Patient-related factors, such as underlying illness for all major sites of infection and advanced age, and pathogen-related factors, such as the ability of bacteria to adhere to epithelial cells, play the major roles in the pathogenesis of colonization. However, exact mechanisms of colonization have not been elucidated, and modulation of bacterial adherence as a method of infection prevention remains experimental. Current methods of infection prevention, therefore, focus either on preventing growth of colonizing microorganisms or on preventing patient-pathogen contact. Topical antibiotics have been used as a method of colonization prevention. However, their effectiveness may be limited by increases in antibiotic resistance; moreover, the effects on patient outcome are controversial. Maintenance of the physiologic mucosal environment using nonantimicrobial agents seems a promising approach, but only a few studies demonstrating efficacy have been published. Prevention of colonization still must rely heavily on basic infection control measures to prevent contact between patient and pathogen.