Febrile neutropenia (FN) is a potentially life-threatening complication of myelosuppressive chemotherapy. The European Organisation for Research and Treatment of Cancer (EORTC) guidelines recommend use of primary granulocyte colony-stimulating factor (G-CSF) prophylaxis if the overall FN risk to a patient is >or=20%, or if a reduction in chemotherapy dose intensity correlates with a poorer outcome. Many of the regimens used for treatment of lymphoma, including R-CHOP (rituximab combined with cyclophosphamide, doxorubicin, vincristine and prednisolone), are associated with an FN risk of approximately 20% or higher. Individual patient factors that may increase the risk of FN such as advanced age or advanced disease should be taken into account when assessing the need for G-CSF support. Predictive models are being developed to facilitate individual risk assessment. Additional anti-infective prophylaxis may be indicated in some settings. There is now much evidence for the benefits of G-CSF in reducing the incidence of FN and facilitating delivery of chemotherapy, including dose-escalated and dose-dense (interval-reduced) regimens. If given according to guidelines, G-CSF has the potential to reduce FN and related morbidity. Furthermore, by facilitating delivery of planned chemotherapy, use of G-CSF may potentially influence survival in the curative setting. Implementation of the EORTC guidelines will lead to a greater proportion of patients receiving G-CSFs, but the costs involved should be at least partly offset by a reduction in FN and its associated costs, including those of hospitalization.