Magnetic resonance (MR) diffusion imaging allows detection of cerebral ischemia within minutes of onset, and the temporal evolution of diffusion characteristics enables differentiation of acute from chronic stroke. T2-weighted MR imaging demonstrates infarcted tissue but fails to demonstrate acutely ischemic regions. Furthermore, the similar signal intensity characteristics of acute and chronic stroke on T2-weighted images limit the ability to determine the acuteness of an infarct. Diffusion imaging thus has tremendous potential for helping direct the treatment of acute ischemic stroke. Controversy exists over the pathophysiology of underlying changes in diffusion and the reversibility of changes after reperfusion in humans. There is also a lack of reproducibility in the time course of diffusion changes between research centers. Use of optimal diffusion imaging strategies results in increased conspicuity of ischemic regions and increased reproducibility of diffusion constants between research centers. An understanding of the principles of diffusion imaging and current controversies in the field is necessary for optimal application of this technique in the evaluation and treatment of cerebral ischemia.