K_ATP channels in pancreatic β-cells couple glucose metabolism with membrane potential to control insulin secretion. Each channel consists of four pore-forming inward rectifier potassium channel subunits Kir6.2, encoded by KCNJ11, and four regulatory subunits sulfonylurea receptor 1  (SUR1), encoded by ABCC8. The total K_ATP channel conductance that determines β-cell membrane potential is dependent on the intracellular ATP- and ADP-regulated channel open probability as well as the number of K_ATP channels in the plasma membrane. Trafficking of K_ATP channels to the β-cell surface requires correct assembly of Kir6.2 and SUR1 in the endoplasmic reticulum (ER). Mutations in the K_ATP channel genes that impair surface expression result in hyperinsulinism and hypoglycemia. Pharmacological inhibitors of K_ATP channels such as sulfonylureas and glinides commonly used to treat type 2 diabetes correct a subset of mutations that disrupt K_ATP channel trafficking to the cell surface. Recent high-resolution K_ATP cryoEM structures provide insights to the structural basis of K_ATP channel assembly and the mechanism by which K_ATP inhibitors overcome channel trafficking defects caused by mutations. Beyond ER, K_ATP channel trafficking is subject to dynamic regulation by physiological signals. The satiety hormone leptin and glucose deprivation both trigger signaling events that upregulate K_ATP trafficking from an endocytic pool to the plasma membrane to dampen β-cell excitability. Elucidation of the structural and signaling mechanisms regulating K_ATP channel trafficking in β-cells uncovers new strategies to manipulate K_ATP channels and thereby insulin secretion to restore glucose homeostasis.