Across the perinatal period, the human brain undergoes a rapid yet highly programmed sequence of maturation. In this time, neural activity has a key role in establishing the brain's early circuits and guiding essential processes including cell differentiation, neuronal and axonal growth, arborization and synaptogenesis. fMRI studies of young infants hold great potential to understand developmental changes in systems-wide activity and their relationship to regional growth and development. These studies have shown that the brain's activity rapidly evolves across the perinatal period, as neurovascular coupling matures and resting state networks are established. The high variability of spatial and temporal properties in functional activity may be attributed to the sensitivity of neurovascular coupling to developing cellular structure and connectivity as well as fluctuations in cerebral physiology, behavioral state, and pathology. Longitudinal studies may precisely explore these relationships and provide mechanistic understanding of the relationship between physiology, behavior, injury, and functional activity.