Microvascular permeability is a pharmacologic indicator of tumor response to therapy, and it is expected that this biomarker will evolve into a clinical surrogate endpoint and be integrated into protocols for determining patient response to antiangiogenic or antivascular therapies. This review discusses the physiological context of vessel permeability in an imaging setting, how it is affected by active and passive transport mechanisms, and how it is described mathematically for both theoretical and complex dynamic microvessel membranes. Many research groups have established dynamic-enhanced imaging protocols for estimating this important parameter. This review discusses those imaging modalities, the advantages and disadvantages of each, and how they compare in terms of their ability to deliver information about therapy-associated changes in microvessel permeability in humans. Finally, this review discusses future directions and improvements needed in these areas.