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Febrile neutropenia causes significant morbidity and mortality in patients receiving cytotoxic chemotherapy. Antibiotic and granulocyte colony stimulating factor prophylaxis reduce the incidence of febrile neutropenia but uncertainty remains regarding their role in clinical practice. We review recent literature to clarify the issue.Recent research confirms that prophylactic antibiotics decrease febrile neutropenia and infection-related mortality in acute leukaemia patients and those receiving high dose chemotherapy. Fluoroquinolone prophylaxis also decreases the incidence of febrile neutropenia and all-cause mortality in the first cycle of moderately myelosuppressive chemotherapy for solid tumours. There is no convincing evidence that colonization of individuals with resistant organisms due to antibiotic prophylaxis increases febrile neutropenia or mortality. Granulocyte colony stimulating factor prophylaxis reduces infection-related mortality in patients with greater than 20% risk of febrile neutropenia.Antibiotic prophylaxis should be offered to patients receiving chemotherapy for acute leukaemia and high dose chemotherapy for solid tumours. It should also be offered to those receiving moderately myelosuppressive chemotherapy for solid tumours and lymphomas during the first cycle of chemotherapy. Prophylactic granulocyte colony stimulating factor is indicated for patients at greater than 20% risk of febrile neutropenia. Further research is indicated to determine whether combining granulocyte colony stimulating factor and antibiotic prophylaxis causes a further reduction in infection-related mortality.