Bacterial infections account for most infections in hematopoietic stem cell transplant recipients. While early mortality reduced dramatically with the introduction of the concept of empirical antibiotic therapy in neutropenic patients, no effect of prophylaxis on the mortality was observed in many studies. On the other hand, antibiotic prophylaxis has resulted in the emergence of resistance among bacteria. In addition, the choice of the antibiotic regimen for empirical therapy and the practices of antibiotic therapy during neutropenia may result in a significant shift in the pattern of bacterial infections. The use of quinolones and vancomycin as prophylaxis, and of carbapenems and vancomycin in the empirical antibiotic therapy, are associated with the appearance of resistant Gram-positive and Gram-negative bacteria. Therefore, hematologists must be aware of the impact of these practices on the emergence of infections due to multi-resistant pathogens, since these infections may be associated with increased mortality.