Insulin-like growth factor I (IGF-I) is a neurotrophic factor that regulates neurogenesis, synaptogenesis, and neuronal survival. It also enhances neuronal activity and facilitates synaptic plasticity. Additionally, IGF-I plays a critical role in the regulation of metabolism in mammals. Emerging evidence indicates that IGF-I modulates sleep architecture. The circadian integration of metabolic and neuronal systems serves to optimize energy utilization across the light/dark cycle. Current data suggest that IGF-I may be a key mediator of this integration, promoting brain activity during wakefulness, a state that coincides with increased metabolic demand. In this review, we summarize recent findings on the interplay between metabolism, IGF-I, and brain activity.