In this review, we discuss molecular brain imaging studies using positron emission tomography (PET) with 2-deoxy-2(18F)fluoro-D-glucose (FDG) in human newborns and infants, and illustrate how this technology can be applied to probe the neuropathophysiology of neonatal neurologic disorders. PET studies have been difficult to perform in sick babies because of patient transportation issues and suboptimal spatial resolution. With approval from the FDA and the institutional review board, we modified and installed the Focus 220 animal microPET scanner (Concorde Microsystems, Knoxville, TN) directly in our neonatal intensive care unit in Children’s Hospital of Michigan and verified the high spatial resolution (<2 mm full-width-at-half-maximum) of this microPET. The neonatal pattern of glucose metabolism is very consistent, with the highest degree of activity in primary sensory and motor cortex, medial temporal region, thalamus, brain stem, and cerebellar vermis. Prior studies have shown that increases of glucose utilization are seen by 2 to 3 months in the parietal, temporal, cingulate, and primary visual cortex; basal ganglia; and cerebellar hemispheres. Between 6 and 8 months, lateral and inferior frontal cortex becomes more functionally active and, eventually, between 8 and 12 months, the dorsal and medial frontal regions also show a maturational increase. These findings are consistent with the physical, behavioral, and cognitive maturation of the infant. At birth, metabolic rates of glucose utilization in cortex are about 30% lower than in adults but rapidly rise such that, by 3 years, the cerebral cortical rates exceed adult rates by more than 2-fold. At around puberty, the rates for cerebral cortex begin to decline and gradually reach adult values by 16-18 years. These nonlinear changes of glucose utilization indirectly reflect programed periods of synaptic proliferation and pruning in the brain. Positron emission tomographic (PET) imaging of GABAA receptors (using 11C-flumazenil) in newborns also show a pattern very different from adults, with high binding in amygdala-hippocampus, sensory-motor cortex, thalamus, brain stem, and basal ganglia, in that order. We speculate that the early development of amygdala/hippocampus prepares the baby for bonding, attachment, and memory, and the deprivation of such experiences during a sensitive period results in malfunction of these networks and psychopathology, as has been shown in studies on severely socioemotionally deprived children. Recently developed hybrid PET/magnetic resonance (MR) scanners allow the simultaneous acquisition of PET and MR data sets with advanced applications. These devices are particularly advantageous for scanning babies and infants because of the high spatial resolution, automated coregistration of anatomical and functional images and, in the case of need for sedation, maximal data acquired in 1 session.