Persistent challenges in managing pulmonary vascular disease progression and poor outcomes, despite the aggressive use of current drug therapies, highlight the need for identifying novel targets for intervention and therapeutic strategies that extend beyond pulmonary vasodilator therapy alone (1). Recent efforts to enhance clinical and molecular phenotyping of patient populations with pulmonary arterial hypertension (PAH) by incorporating “precision medicine” strategies through genetics, genomic and proteomic biomarkers, technologies that enhance right ventricular assessments and lung vascular imaging, and other methods, have generated much excitement that will likely improve patient outcomes (2–5). In addition, a key contributor to morbidity is the relatively late diagnosis in many patients with PAH, whose disease is not recognized until the onset of clinical signs and symptoms, when substantial pulmonary vascular disease is already present. Thus, a contemporary focus in PAH is on early identification and intervention of at-risk patients before the development of significant pulmonary vascular disease (2). Conclusions from large epidemiologic studies in unselected patients cast new light on the spectrum of risk associated with cardiopulmonary hemodynamics. These reports identify a sizeable population that appears vulnerable clinically due to pulmonary arterial pressure that is minimally elevated but below the currently accepted range of abnormal (6, 7). This trend reiterates the importance of focus on pulmonary hypertension before end-stage disease and in this way parallels pivotal clinical trial data in patients with idiopathic PAH (8) and systemic sclerosis (SSc)-associated PAH (9) that favor early and aggressive therapeutic intervention to improve outcome. Furthermore, converging observations reporting on the mechanisms underlying pediatric and adult PAH have begun to identify previously unrecognized genetic, molecular, and developmental factors that predict future or adult-onset PAH, including preeclampsia (PrE), chorioamnionitis, and placental insufficiency with intrauterine growth restriction (10–13)(Figure 1). Collectively, these advances set the framework for a new and potentially transformative era in pulmonary hypertension in which preventative medicine and patientspecific therapies are a principal emphasis.