Fuchs endothelial corneal dystrophy (FECD) is a progressive and debilitating disorder of the corneal endothelium (CE) that affects approximately 4% of individuals over the age of 40. Despite the burden of the disease, the pathogenesis of FECD remains poorly understood, and treatment options are limited, highlighting the need for deeper investigation into its underlying molecular mechanisms. Over the past decade, studies have indicated independent contributions of endoplasmic reticulum (ER) and mitochondrial stress to the pathogenesis of FECD. However, there are limited studies suggesting ER-mitochondria crosstalk in FECD. Recently, our lab established the role of chronic ER stress in inducing mitochondrial dysfunction for corneal endothelial cells (CEnCs), indicating the existence of ER-mitochondria crosstalk in FECD. This paper aims to provide a comprehensive overview of the current understanding of how ER and mitochondrial stress contribute to FECD pathogenesis. The paper also reviews the literature on the mechanisms of ER-mitochondria crosstalk in other diseases relevant to FECD.