In modern therapy of malignant diseases intensive chemotherapy is widely used, and the standard approach is also high-dose chemotherapy with autologus and allogeneic stem cell transplantation. Such treatment is usually followed by development of neutropenia, while infection occurrence in a neutropenic patient is a potentially lethal complication of therapy. During last several years risk factors for developing infection in neutropenic patients have been defined; patients can be categorized as high or low risk. Low risk patients can be treated with oral antibiotics in outpatient conditions. High risk patients should receive wide spectrum antibiotics, possibly in combination with aminoglycoside. Vancomycin should be given if soft tissue or catether infection is suspected, or if gram-positive agent has been isolated. The approach to a neutropenic patient with fever should be individualized, adjusted to specific patient characteristics, health care organization and specific microbiology environment in the treating hospital.