The pathogenesis of pulmonary arterial hypertension (PAH) is complex, involving multiple modulating genes and environmental factors. Multifactorial impairment of the physiologic balance can lead to vasoconstriction, vascular smooth muscle cell and endothelial cell proliferation/fibrosis, inflammation, remodeling and in-situ thrombosis. These are the likely mechanisms that lead to narrowing of the vessel followed by progressive increase in pulmonary vascular resistance and the clinical manifestations of pulmonary hypertension. Subsequently, major goal of the therapy is to avoid acute pulmonary vasoconstriction, halt the progression of vascular remodeling, and reverse the early vascular remodeling if possible. Recently published data addressing certain molecular mechanisms for pathogenesis of PAH have led to the successful therapeutic interventions. This review will focus on the common and critical molecular pathways including genetic basis of the development of PAH that on the whole may be new targets for therapeutic interventions.