As cancer chemotherapy became more popular for treating patients with solid tumors, the clinical pattern of febrile neutropenia (FN) progressively changed and it became accepted that all patients with FN do not necessarily share the dismal prognosis seen in leukemic FN patients earlier in the 1960s [1]. The perception of the heterogeneity of the population of patients with FN led to the concept of risk evaluation to tailor the therapeutic approach to these patients. The most effective scoring system for the evaluation of the risk of severe complications and death in patients with FN has been developed by the Multinational Association for Supportive Care in Cancer (MASCC) Infection Study Group [2] and has been validated in many studies, both in patients with solid and hematological tumors [3]. Its use has been recommended by international organizations such as the European Society of Medical Oncology (ESMO) and Infectious Diseases Society of America (IDSA) [4, 5]. The availability of a predictive tool for the prognosis of patients with FN allows a new algorithm for the initial management of FN, as summarized in Fig. 1. Indeed, the calculation of the MASCC score, upon the presentation of the patient with FN, can separate between those patients with low risk of complications (less than 5 %) and death (less than 1 %) and those with an increased risk, leading to the different therapeutic options. However, it should be emphasized that FN is always a medical emergency, as the progression from a relatively stable condition into overwhelming sepsis may be fulminant; this is why it is recommended that the administration of antibiotics to a patient presenting with FN should be initiated within 60 min [6].