The autochthonous anaerobic bacterial flora in the mucosal layer of the gastrointestinal tract limits colonization by aerobic potential pathogens. This effect is called colonization resistance. Colonization of the digestive tract by potentially pathogenic microorganisms precedes infection in patients with leukopenia and in cases of mechanical ventilation and can be prevented by long-term administration of antimicrobial agents that spare the autochthonous anaerobic bacterial flora of the mucous membranes, a concept known as selective decontamination. Antimicrobial agents active against anaerobic flora reduce colonization resistance, permitting colonization by and overgrowth of potentially pathogenic microorganisms and possibly leading to infections with resistant microorganisms. A distinction can be made between antimicrobial agents that reduce colonization resistance and those that leave it intact by examining the effect of antimicrobial agents on aerobic intestinal flora of mice and humans.