INTRODUCTION Oxygen saturation monitors or pulse oximeters (SpO2) were entered into practice in the 1980s not only without randomized trials but also, and probably more importantly, without education of neonatal bedside care providers around the world (i. e.: nursing staff, respiratory therapists and also physicians). Education about some known physiological principles, such as the changing relation between O2 and hemoglobin, PaO2 and O2 saturation (O2Sat), did not accompany the routine implementation of SpO2 monitors. Preterm infants of all gestational ages and postnatal ages receiving supplemental oxygen have been treated in many places using targets of O2Sat seen in normal healthy infants breathing room air (i. e.: “physiological” or “normal” values). This was accepted and entered into practice in many cases without full understanding of the meaning of what O2Sat really is and without considering the changing relationship between PaO2 and O2Sat and the differences in SpO2 monitors used. In the past few years, the findings in a number of studies have shown that the long-accepted “physiological” targets of O2Sat by many may in fact be too high. However a “comfort zone” exists in routine clinical practice and it is assumed that if the O2Sat is “high” and the baby appears pink, the preterm baby is “doing well”. On the other hand, in many units, based on understanding of known and proven concepts, the targets of O2Sat were never 97-100 % for preterm infants receiving supplemental oxygen early in life. Oximetry monitors have become commonplace in acute healthcare setting over the last 10-12 years. It has been said blood oxygen can now be considered a “fifth vital sign”. By 1989 there were 29 manufacturers producing 45 different models of oximeters1. There are currently less manufacturers producing over 20 different models and recent technological advances have changed some important aspects of SpO2 performance. All SpO2 monitors have some variability between the measurements with the actual arterial O2Sat value measured by a cooximeter, but true new generation SpO2 monitors are much better than all others. As importantly, monitors are affected by noise, but the different SpO2 monitors handle noise in different ways, leading to differences in real measurements, speed in which a problem is detected, alarms and false alarms, and the presence or not of “holding periods”. In addition, newer technology offers measurements of perfusion index. It is our objective to describe all these factors and others in relation to SpO2 monitoring for neonates. The reliability, accuracy and therefore clinical utility of pulse oximetry remain problematic in some types of infants under certain conditions. As it will be described in this manuscript, improved signal processing technology has substantially improved the ability of some oximeters to work reliably under conditions of poor perfusion, motion artifact and noise from other sources such as bilirubin lights. Historically it was common teaching that if clinicians or bedside care providers were confronted with questionable oxygen saturation values, they should estimate the reliability of the monitor by correlating the pulse rate measured by the oximeter with the heart rate obtained by an electrocardiogram (ECG) monitor used simultaneously. As it will be shown later, accuracy in the recording of pulse rates is also a problem of many monitors.