Abstract Several prospectively randomized trials have shown that the administration of prophylactic oral nonabsorbable antibiotics may be beneficial in decreasing the incidence of infection in granulocytopenic patients, whereas others have not. Intolerable nausea and vomiting have prevented the prolonged use of these agents in some studies. Discontinuation of therapy while patients are still granulocytopenic has carried the risk of life-threatening infections, often with aminoglycoside-resistant gram-negative organisms. The benefit of selective decontamination with trimethoprim/sulfamethoxazole used prophylactically remains controversial. The use of trimethoprim/sulfamethoxazole may also be associated with the development of resistant, potentially pathogenic, organisms or prolonged neutropenia. These regimens do not appear to be indicated when patients are anticipated to be neutropenic for less than three weeks. Even in patients with prolonged neutropenia, the risks of such treatment must be weighed against potential benefits.