During the past 10 years the concepts of total reverse isolation using laminar air flow rooms and alimentary canal microbial suppression using oral nonabsorbable antibiotics have each been proved effective in reducing serious infection for patients with profound, prolonged granulocytopenia. When these two modalities are combined, the net reduction in infections is about 75%. Oral nonabsorbable antibiotics, however, are poorly tolerated, costly, and frequently associated with the acquisition of resistant gram-negative rods when used outside the laminar air flow room setting. The concept of colonization resistance may be the new approach needed for microbial suppression of the nonisolated patient. If the anaerobic flora is undisturbed, newly acquired organisms generally cannot colonize the patient. Agents such as trimethoprim/sulfamethoxazole suppress many of the potentially pathogenic aerobic bacteria but not the anaerobes, leaving colonization resistance relatively intact. The result thus far has been a reduction in infection without a concurrent increase in colonization or infection by organisms resistant to the antimicrobial agents commonly used for therapy.