Functional lung imaging has the potential to offer many new insights into mechanisms of pulmonary disease. While the physiologist has access to a number of techniques to evaluate lung function, such as multiple inert gas elimination technique or the injection of microspheres, these techniques have significant disadvantages, including lack of spatial information or low spatial resolution and, in the case of microspheres, an inability to make measurements in humans. The functional imaging techniques based on magnetic resonance (MR), computed tomography (CT), or positron emission tomography (PET) hold substantial promise. In this article, specific issues related to the MR evaluation of pulmonary blood flow, including quantification of heterogeneity, reliability, and validity of the technique, are discussed to highlight some of the important physiologic issues that affect functional imaging. Additional physiologic considerations include the anatomic partitioning of blood flow, and the effects of posture, breath holding, and exercise. The relationships between these many factors and the collection of regional pulmonary perfusion data are explored.