Pulmonary hypertension (PH) is initially a disease of the small, peripheral resistance arteries. Changes in these vessels are best assessed by measurement of pulmonary artery pressure at several levels of flow to generate multi-point pressure-flow curves. This approach is superior to the traditional single-point measurement of pulmonary vascular resistance (PVR) because it allows a flow-independent definition of the resistive properties of that portion of the pulmonary vascular bed and also provides information on its distensibility. In animal models, multi-point pressure-flow curves can be obtained using an isolated, ventilated, perfused lung system. Clinically, cardiopulmonary exercise testing (CPET) with non-invasive echocardiography is feasible and provides realistic values of the resistance and peripheral compliance. Together, these values can be used to better understand and screen for PH and exercise-induced PH.