It has long been thought that the prefrontal cortex, as the seat of most higher brain functions, is functionally silent during most of infancy. This review highlights recent work concerned with the precise mapping (localization) of brain activation in human infants, providing evidence that prefrontal cortex exhibits functional activation much earlier than previously thought. A systematic evaluation of the activation patterns in these neuroimaging studies mainly based on functional near-infrared spectroscopy reveals that prefrontal cortex function can be broadly divided into two distinct anatomical clusters with different functional properties. One cluster of activations falls within the region of the medial prefrontal cortex and is mainly involved in affective processes; another cluster is located in lateral aspects of the prefrontal cortex and shows sensitivity to cognitive processes such as memory and attention. This distinction is in line with adult data and evolutionary models and may represent a developmentally continuous organization principle of prefrontal cortex function. All in all, this review is aimed at providing a synthesis of new findings that are emerging from the use of neuroimaging techniques with infants as well as at encouraging further theory-driven research to understand the developmental origins of prefrontal cortex function.