Glucose is an essential fuel for the brain, and its concentration must be maintained within strict boundaries for optimal fitness. Maintaining glucose homeostasis involves a balance between glucose uptake and output, as well as the management of daily rhythms in glucose concentrations. This chapter explores the roles of various brain regions in glucose homeostasis and their connections through the sympathetic and parasympathetic nervous systems to peripheral organs such as the pancreas and liver. Key hypothalamic nuclei, including the arcuate nucleus and the ventromedial hypothalamus, are well established in their roles in glucose regulation. Additionally, cortico-limbic areas, such as the nucleus accumbens and amygdala, contribute to the modulation of glucose metabolism. These brain regions communicate with the pancreas and liver via autonomic pathways, influencing insulin secretion, hepatic glucose production, and overall metabolic balance. By examining the neural circuits and mechanisms involved, this chapter aims to provide a comprehensive understanding of how brain-body interactions maintain glucose homeostasis and their implications for metabolic health.