This article describes the basic physics of dissolution dynamic nuclear polarization (dissolution‐DNP), and the impact of the resulting highly nonequilibrium spin states, on the physics of magnetic resonance imaging (MRI) detection. The hardware requirements for clinical translation of this technology are also presented. For studies that allow the use of externally administered agents, hyperpolarization offers a way to overcome normal magnetic resonance sensitivity limitations, at least for a brief T1‐dependent observation window. A 10,000–100,000‐fold signal‐to‐noise advantage provides an avenue for real‐time measurement of perfusion, metabolite transport, exchange, and metabolism. The principles behind these measurements, as well as the choice of agent, and progress toward the application of hyperpolarized 13C metabolic imaging in oncology, cardiology, and neurology are reviewed. J. Magn. Reson. Imaging 2012; 36:1314–1328. © 2012 Wiley Periodicals, Inc.