Understanding the mismatching of ventilation and perfusion (VA/Q) is of special interest in the intensive care setting because - given a stable cardiac output and a given inspiratory oxygen fraction - it allows one to explain certain essential respiratory problems in critically ill patients, namely hypoxemia and hypercarbia. Several different methods are available today for the evaluation VA/Q mismatching. Analysis of the PCO2 and PO2 in arterial and mixed venous blood and mixed expired gas yields information about the quality and the degree of the mismatching present. Calculation of the physiologic dead space (VD/VT) and venous admixture (QVA/QT) from the PCO2 and PO2 data allow the VA/Q mismatching to be quantified according to a three-compartment model of the lung. Determination of the arterial-alveolar nitrogen partial-pressure difference permits a more precise estimation of the true right-to-left shunt as a cause of arterial hypoxemia, but the measurement of the arterial PN2 remains a delicate procedure. The multiple inert gas elimination technique permits virtually continuous ventilation-perfusion distributions to be described over the whole range of VA/Q ratios and has contributed to explaining the pathophysiological mechanisms in various pulmonary diseases. This method, however, is technically very complex and hence will remain a sophisticated investigational tool. Scintigraphic approaches allow the description of regional topographic VA/Q distributions, but their application is still difficult in the intensive care setting.