Advanced pulmonary arterial hypertension is characterized by extensive vascular remodeling that is usually resistant to vasodilator therapy. As the major component of the vascular media, decreased apoptosis of pulmonary arterial smooth muscle cell (PASMC) plays key roles during pulmonary vascular remodeling. Recent studies showed that enhancement of apoptosis of PASMC can reverse pulmonary vascular remodeling and severe pulmonary arterial hypertension. Enhancement of apoptosis of PASMC is becoming a novel strategy to reverse severe pulmonary arterial hypertension. This review analyzes some potential strategies to reverse pulmonary vascular remodeling.