Drugs targeting control of metabolism by the CNS act mainly via homeostatic and hedonic control centers that govern feeding behaviors, energy and glucose homeostasis, and body weight. The related brain areas are densely interconnected, and receive direct input from circulating nutrients such as glucose or fatty acids, peripheral neuronal networks, and hormonal satiation signals such as GLP-1 or amylin, or hormonal adiposity signals such as leptin. Within the homeostatic and hedonic control centers, the peripheral signals are integrated with sensory input, past experiences, and cues arising from the prevailing stress situation, emotional context, and mood. Ultimately, the signals converge in nuclei such as the hypothalamic paraventricular nucleus and lateral hypothalamus, and induce both adaptations to our ingestive behavior and brain stem–mediated changes to peripheral organ functions and our control of energy and glucose metabolism. AP, area postrema; ARC, arcuate nucleus; FGF21, fibroblast growth factor 21; GI tract, gastrointestinal tract; GIP, glucose-dependent insulinotropic polypeptide; GLP-1, glucagon-like peptide-1; LH, lateral hypothalamus; NAc, nucleus accumbens; NTS, nucleus of the solitary tract; PVN, paraventricular nucleus; PYY3-36, peptide YY 3-36; VTA, ventral tegmental area.