Despite recent advances in the management of patients with pulmonary arterial hypertension (PAH), this disease remains a devastating condition with limited survival. While the current therapies primarily target the vasoconstrictor/vasodilator imbalance in the pulmonary circulation, there is currently no cure for PAH, and pulmonary vascular remodeling-representing the underlying cause of the disease-is only modestly affected. Hence, novel therapeutic approaches directly targeting the vascular remodeling process are warranted. Recent studies provided compelling evidence that peptide growth factors, which elicit their signals via receptor tyrosine kinases, are important contributors to the development and progression of PAH. In particular, platelet-derived growth factor (PDGF) is a strong mitogen for pulmonary vascular smooth muscle cells and protects these cells from apoptosis, thus representing an important mediator of pulmonary vascular remodeling. PDGF ligand and receptors are upregulated in PAH, and experimental studies have shown that inhibition of PDGF receptor signaling by pharmacological or genetic approaches prevents the development of PAH in animal models and is even able to reverse pulmonary vascular remodeling once it has been established. Consistently, results from phase II and phase III clinical trials indicate that the tyrosine kinase inhibitor imatinib mesylate, which potently inhibits the PDGF receptor, is effective in improving exercise capacity and pulmonary hemodynamics as add-on therapy in patients with severe PAH (i.e., pulmonary vascular resistance >800 dynes s cm(-5)). Future studies will evaluate the long-term clinical efficacy and safety of imatinib, including patients with less impaired hemodynamics. Based on the current knowledge, targeting of PDGFR signaling is likely to become an anti-proliferative treatment option for patients with PAH and has the potential to at least partially correct the pathology of the disease.