This article provides a review of cerebral tissue oxygenation during immediate transition after birth in human neonates. Recommended routine monitoring, especially if resuscitation is needed, during this period includes arterial oxygen saturation and heart rate measured by pulse oximetry and electrocardiogram. However, there is increasing interest to monitor in addition with near-infrared spectroscopy (NIRS) the oxygenation of the brain. There is a different pattern of increase between cerebral tissue oxygenation and arterial oxygen saturation during the immediate transition, with cerebral tissue oxygenation reaching a plateau faster than arterial oxygen saturation. Differences can be explained, since cerebral tissue oxygenation is not only affected by arterial oxygen saturation but also by cerebral blood flow, hemoglobin content, and cerebral oxygen consumption. Normal values have already been established for different devices, gestational ages, and modes of delivery in neonates without any medical support. Cerebral hypoxia during immediate transition might cause brain damage. In preterm neonates with cerebral hemorrhage evolving in the first week after birth, the cerebral tissue oxygenation is already lower in the first minutes after birth compared to preterm neonates without cerebral hemorrhage. Using cerebral NIRS in combination with intervention guidelines has been shown to reduce the burden of cerebral hypoxia in preterm neonates. Cerebral tissue oxygenation during immediate transition seems to have an impact on outcome, whereby NIRS monitoring is feasible and has the advantage of continuous, non-invasive recording. The impact of NIRS monitoring and interventions on short- and long-term outcomes still need to be evaluated.