It appears that the use of antibiotic combinations, especially synergistic ones, is indicated for the management of gram-negative bacillary sepsis in granulocytopenic patients. Synergism is a valuable factor in increasing the serum bactericidal activity, which is highly likely to be important for a favorable outcome in these infections. The potential side effects of antimicrobial combinations should not deter clinicians from their use. The most frequently used combinations for gram-negative bacillary infections are those involving beta-lactams and aminoglycosides. Other potentially synergistic combinations exist as well; however, the clinical experience with these combinations is limited, and, as with double beta-lactam combinations, their potential for antagonism necessitates care when using them. Besides gram-negative bacillary sepsis in granulocytopenic patients, severe staphylococcal infections might represent an indication for the use of combination therapy, especially in patients with compromised mechanisms of defense against infection.