Studies in the past decade have demonstrated that endoplasmic reticulum (ER) stress is closely associated with pathogenesis of hypertension. Signaling pathways involving AMP-activated protein kinase (AMPK) and NADPH-oxidase (Nox) have been identified to regulate ER stress; whilst ER stress contributes to the imbalance production between nitric oxide (NO) and reactive oxygen species (ROS). The present article reviews the protective effects and the potential therapeutic implication of ER stress inhibition by drugs or natural products in hypertension.