Many oncologists are considering granulocyte colony-stimulating factor (G-CSF) a drug of mainly benefits with only few and minor side effects for patients with neutropenia following treatment with myelosuppressive chemotherapy. In a retrospective study, Volpi and colleagues (page 2514) describe significant long-term cellular immune impairment of T cells in patients treated after HLA haplotype–mismatched hematopoietic stem-cell transplantations with G-CSF to reduce the period of neutropenia and improve engraftment after transplantation. The benefits shortly after transplantation appeared to be minor, whereas the long-term immune dysregulation may be significant, as illustrated by the reduced capacity of T cells to cope with fungal infections. Thus far, these findings could not be translated into a significant difference in clinical outcome. The authors also show that G-CSF treatment may have a negative influence on the in vitro immune functions in normal donors treated with G-CSF to mobilize stem cells for transplantation. This raises the question of whether long-term immune functions have been sufficiently monitored in these volunteers to conclude that G-CSF–induced mobilization of stem cells is without significant health risks for the donor. Furthermore, the use of G-CSF in many patients treated with relatively low doses of chemotherapy resulting in only short-term neutropenia may have to be reevaluated. Although the numbers of days of neutropenia or hospitalization can be reduced, possible late cellular immune dysfunction has not been addressed in most clinical studies. The report by Volpi and colleagues indicates that the long-term immunologic effects of G-CSF should be monitored and that new prospective randomized studies may be necessary to allow a balanced assessment of the short-term benefits against potential long-term risks.