The pancreatic β-cell senses nutrients, neurotransmitters and hormones in the circulating blood. The unique function of the cell is to integrate all these ambient signals into an appropriate insulin secretory rate in order to maintain normal glucose homeostasis. A prerequisite for adequate insulin secretion is proper biosynthesis of the hormone. The rate of biosynthesis needs to be regulated in order to compensate for rapid fluctuations in secretory rate. The synthesis of insulin includes transcription of its gene to mRNA, translation of mRNA into preproinsulin, and processing of preproinsulin via proinsulin into mature insulin. It also involves the induction of additional components of the secretory pathway to support processing, transport and exocytosis of insulin granules. The endoplasmic reticulum (ER) is the cell organelle playing a paramount role in these processes. A functional ER is crucial to all eukaryotic cells, but especially important in a professional hormone-secreting cell like the β-cell. This essay will describe the phenomenon of ER stress in pancreatic β-cells with special focus on its involvement in the regulation of β-cell survival and death. The involvement of some ER stress components in the regulation of insulin biosynthesis and secretion will be discussed, along with a short description of the ER stress response (also known as the unfolded protein response).