Bacterial sepsis is a major cause of neonatal morbidity and mortality. Successful management of neonatal sepsis requires early diagnosis, appropriate antimicrobial treatment, and aggressive intensive care. However, even when steps are taken appropriately, mortality rates can be high, particularly among certain subgroups, such as extremely preterm neonates and neonates with neutropenia. Multiple factors contribute to the increased susceptibility of neonates to infection, including developmental quantitative and qualitative neutrophil defects. Studies of infected animal and human neonates suggest that the use of recombinant human granulocyte colony stimulating factor (rhG-CSF) or recombinant human granulocyte macrophage colony stimulating factor (rhGM-CSF) can partially counterbalance these defects and thereby reduce morbidity and mortality. However, the body of clinical evidence is currently not sufficient to recommend rhG-CSF or rhGM-CSF administration confidently as routine adjunctive treatment for neonates with sepsis.