Abstract: Endoplasmic reticulum (ER) is an organelle involved in protein folding, calcium homeostasis and lipid biosynthesis. Various factors can lead to the accumulation of unfolded proteins including oxidative stress, ischemia and disturbance of calcium homeostasis, which will trigger the unfolded protein response (UPR) by chaperons in the ER to promote cellular survival. However, if stress is severe, ER stress (ERS) also initiates apoptotic signaling to lead to cell death via mitochondria-dependent and -independent apoptotic pathways. Thus, ER is now recognized as a vitally important organelle that can decide cell survival or death. Recent studies have revealed that ERS is related to the pathophysiology of various cardiovascular diseases such as heart failure and ischemic heart disease. A better understanding of molecular mechanisms will provide us with new targets for drug discovery and therapeutic intervention. This article will make an introduction of ERS and its relationship with cardiovascular diseases.