The endoplasmic reticulum (ER) is the key cellular organelle involved in protein homoeostasis. The unfolded protein response (UPR) is a fundamental cellular process triggered by ER stress because of lack of ATP or primary ER dysfunction. The UPR is activated and dysregulated in non-alcoholic fatty liver disease (NAFLD). The UPR has been shown to be involved in both normal physiologic functions and the cellular response to a host of pathologic states. This article reviews the pathways by which the UPR unfolds and its potential role in the development and progression of NAFLD.