The pancreas is the primary organ responsible for the digestion of food. Pancreatic acinar cells are specialized for the production of digestive enzymes, and these cells have a higher rate of protein synthesis than all other adult human tissues. Digestive enzymes are produced in the endoplasmic reticulum (ER), a multifunctional organelle responsible for the synthesis and correct folding of proteins in the secretory pathway. Disturbances of ER function lead to stress-response mechanisms that can restore homeostasis but can also, if uncontrolled, cause disease. Pancreatic acinar cells are particularly susceptible to ER perturbations, and mechanisms that relieve ER stress are necessary for normal pancreatic development. Furthermore, ER stress occurs during acute pancreatitis, and may also be present in pancreatic cancer. However, the specific roles of ER stress-response mechanisms in these diseases are unknown.