Pancreatic β-cells are specialized for the production and regulated secretion of insulin to control blood-glucose levels. Increasing evidence indicates that stress-signaling pathways emanating from the endoplasmic reticulum (ER) are important in the maintenance of β-cell homeostasis. Under physiological conditions, ER stress signaling has beneficial effects on β-cells. Timely and proper activation of ER stress signaling is crucial for generating the proper amount of insulin in proportion to the need for it. In contrast, chronic and strong activation of ER stress signaling has harmful effects, leading to β-cell dysfunction and death. Therefore, to dissect the molecular mechanisms of β-cell failure and death in diabetes, it is necessary to understand the complex network of ER stress-signaling pathways. This review focuses on the function of the ER stress-signaling network in pancreatic β-cells.