Since the discovery of three major pathophysiological mechanisms of pulmonary arterial hypertension (PAH), including prostacyclin, endothelin and nitric oxide pathways, the therapeutic options for PAH have increased. Nevertheless, despite these advances, the prognosis remains unsatisfactory for many patients with PAH. With the progress of both pre-clinical and clinical research on PAH, several novel therapeutic targets have been identified for the treatment of PAH. In this study, we review updated information of novel pathophysiological pathways of pulmonary hypertension, mainly focusing on WHO Group I PAH. Drugs based on these pathways are currently under clinical or pre-clinical investigation, however they have been approved for clinical use. Large clinical trials are required to validate the clinical safety and effects of these novel therapies.