Aberrant transforming growth factor-β (TGF-β) signaling activation is linked to pulmonary arterial hypertension (PAH). BMPR2 mutations perturb the balance between bone morphogenetic protein (BMP) and TGF-β pathways, leading to vascular remodeling, narrowing of the lumen of pulmonary vasculature, and clinical symptoms. This forum highlights the association of the TGF-β pathway with pathogenesis and therapeutic approaches.