Granulocytopenic patients are at high risk for infections caused by gram-negative bacteria mostly originating from the gastro-intestinal tract. Several antimicrobial prophylactic regimens are used for prevention of bacterial infections. Prophylaxis with absorbable antimicrobial agents such as trimethoprim-sulfamethoxazole or new fluorinated quinolones seems to be superior to non-absorbable drugs such as polymyxin, vancomycin and gentamicin. The most promising results are obtained with new quinolones. Use of prophylaxis in neutropenic patients leads to changes in the spectrum of infections from gram-negative towards gram-positive.