The brain relies on glucose for fuel but has limited storage capacity. To facilitate adequate glucose availability, the brain senses glucose, initiates feeding behaviour, and controls system glucose metabolism. To date, the majority of studies investigating the sensing and central control of glucose have focused on the hypothalamus and the brainstem. However, recent findings have revealed an unexpected and fascinating role for the striatum, a brain nucleus mainly known for its role in reward behaviour, in glucose homeostasis. I will present a series of experiments, in both humans and rodents, supporting the regulation of peripheral glucose metabolism by striatal dopamine signaling. With rodent studies we also unraveled the neural route via which the striatum, and especially the nucleus accumbens shell, communicates with the liver to regulate glucose production.