Neutrophilic granulocytes express their Fcgamma receptor, also known as the CD64 antigen, predominantly when they are activated. This makes neutrophil CD64 a potential biomarker for infection and sepsis. Indeed there is ample literature on the diagnostic utility of neutrophil CD64 in a variety of diseases. This review summarizes the literature on its application as a sepsis biomarker, in adults as well as in neonates and infants. The available data indicate that neutrophil CD64 seems to have high sensitivity (86%) and specificity (87%), but the methodological quality of most studies is questionable. Nevertheless, neutrophil CD64 appears to be a better diagnostic test than traditional hematological assays, C-reactive protein and probably even procalcitonin. Application of neutrophil CD64 in other conditions than sepsis is briefly presented. Finally, future clinical studies are discussed which are needed in order to confirm the diagnostic performance of this promising biomarker.