In order to take the best approach to infection in the oncohematologic patient with fever, it is important to know not only how profound the neutropenia is and how long the patient has had it, but also the characteristics of the underlying disease, the immunosuppressive therapy received and the type of hematopoietic stem/progenitor cell transplantation performed. Moreover, is important to consider if these patients have any personal or familial history of infectious diseases. All these aspects let us calculate the net state of immunosuppression and the risk of infection, and provide us with information about the most probable etiology in each case and the best prophylaxis and treatment. In this study we review the more important advances in chemotherapy in recent years that will make it necessary in the future to change our prophylactic guidelines for more effective prevention of infection in the oncohematologic patient.