Positron emission tomography (PET) imaging is a noninvasive, quantitative method to assess pulmonary perfusion and ventilation in vivo. The core of this article focuses on the use of [13N]nitrogen (13N2) and PET to assess regional gas exchange. Regional perfusion and shunt can be measured with the 13N2-saline bolus infusion technique. A bolus of 13N2, dissolved in saline solution, is injected intravenously at the start of a brief apnea, while the tracer kinetics in the lung is measured by a sequence of PET frames. Because of its low solubility in blood, virtually all 13N2 delivered to aerated lung regions diffuses into the alveolar airspace, where it accumulates in proportion to regional perfusion during the apnea. In contrast, lung regions that are perfused but are not aerated and do not exchange gas (i.e., "shunting" units) do not retain 13N2 during apnea and the tracer concentration drops after the initial peak. Accurate estimates of regional perfusion and regional shunt can be derived by applying a mathematical model to the pulmonary kinetics of a 13N2-saline bolus. When breathing is resumed, specific alveolar ventilation can be calculated from the tracer washout rate, because 13N2 is eliminated almost exclusively by ventilation. Because of the rapid elimination of the tracer, 13N2 infusion scans can be followed by 13N2 inhalation scans that allow determination of regional gas fraction. This article describes insights into the pathophysiology of acute lung injury, pulmonary embolism, and asthma that have been gained by PET imaging of regional gas exchange.