Almost 90% of extremely low birthweight infants receive red blood cell (RBC) transfusion during their stay in the neonatal unit (NNU). Currently most NNUs use a combination of clinical signs and laboratory findings such as hemoglobin (Hb), hematocrit (Hct), and cardiorespiratory or ventilation status to decide the need for RBC transfusion. Various other laboratory (lactate, reticulocyte count, RBC volume) and bedside measurements (near infrared spectroscopy and Doppler ultrasound scan) have been investigated to identify a suitable trigger for RBC transfusion in newborn infants. The evidence to apply any of these investigations or measurements to clinical practice is lacking. Further research is required to identify a suitable biomarker for RBC transfusion in newborn infants.