Pulmonary hypertension is a fatal disease of which pulmonary vasculopathy is the main pathological feature resulting in the mean pulmonary arterial pressure higher than 25 mmHg. Moreover, pulmonary hypertension remains a tough problem with unclear molecular mechanisms. There have been dozens of studies about endoplasmic reticulum stress during the onset of pulmonary hypertension in patients, suggesting that endoplasmic reticulum stress may have a critical effect on the pathogenesis of pulmonary hypertension. The review aims to summarize the rationale to elucidate the role of endoplasmic reticulum stress in pulmonary hypertension. Started by reviewing the mechanisms responsible for the unfolded protein response following endoplasmic reticulum stress, the potential link between endoplasmic reticulum stress and pulmonary hypertension were introduced, and the contributions of endoplasmic reticulum stress to different vascular cells, mitochondria, and inflammation were described, and finally the potential therapies of attenuating endoplasmic reticulum stress for pulmonary hypertension were discussed.