OBJECTIVES: A literature review was conducted to identify risk factors and predictors of chemotherapy-related grade 3-4 and/or febrile neutropenia to assist with assessing who might benefit from treatments such as prophylactic G-CSF. METHODS: The literature review included publications from 1990-2000 of adults with any tumor type; 121 articles were identified that referenced risk factors or predictors for severe/febrile neutropenia. Study design, patient characteristics, chemotherapy treatment, and incidences of neutropenia were recorded. RESULTS: Twenty-one relevant publications, including prospective, retrospective, and modeling studies, were further analyzed. These articles yielded 27 potential risk factors/predictors in 3 categories: patient (n=14), treatment-related (n=8), and disease-related (n=5) characteristics. Although most of the 27 potential risk factors/ predictors were not validated to identify patients at higher risk for severe/febrile neutropenia, the review suggests that several simple-to-use and commonly available risk factors may be reliable predictors of neutropenia. These included low hemoglobin and neutrophil counts in cycle one; depth of the neutrophil nadir; low lymphocyte, monocyte and platelet levels; and a precipitous, early drop in blood cell counts. Several other risk factors, such as serum albumin < 3.5g/dL on day 1, serum LDH >1x normal alone or combined with bone marrow involvement, and high dose chemotherapy, also warrant further investigation. CONCLUSIONS: Few studies have explicitly explored risk factors associated with the occurrence of Grade 3-4 neutropenia. However, this literature review identified several common characteristics that may be measured with early and frequent CBC monitoring and may reasonably predict predisposition of patients to severe/febrile neutropenia.