Since its initial description, pulmonary arterial hypertension (PAH) has been considered a vascular disease exclusive to the lungs. However, recent studies have uncovered evidence that patients with PAH also demonstrate abnormalities in the systemic circulation that compound the clinical impact of the lung disease. Understanding the nature of this crosstalk between pulmonary and systemic circulation promises to open exciting possibilities not only to understand the mechanisms behind vascular dysfunction but also revise our approach to patient care in PAH.