Diffusion-weighted imaging (DWI) is a relatively new magnetic resonance imaging (MRI) technique that can be used to probe the microenvironment of water. Contrast in DWI depends on properties different from traditional T1 and T2 contrast, and is derived form the translational motion of water molecules. Since it is reasonable to think that a change in the microenvironment of water might be reflected in a change in water diffusion characteristics, the quantitative assessment of the (apparent) diffusion coefficient ADCw may represent a unique means of assessing tissue status. DWI has already shown great utility in the study of cerebral ischemia in animal models and has proved useful in the early identification of cerebral ischemia in patients. More recent reports have indicated a potential for DWI in studying epilepsy. Here, we briefly review some of what is known about the measurement of ADCw in ischemia and compare these results with what has recently been reported for epilepsy. In this manner we hope to better understand the underlying mechanisms behind changes in water diffusion associated with specific pathologies.