Multiple pathologic conditions can cause changes in the random movement of water, which can be detected with diffusion-weighted imaging (DWI). DWI plays a powerful clinical role in detecting restricted diffusion associated with acute brain infarction. Other disorders can also result in restricted diffusion. This article focuses on showing examples of common and uncommon disorders that have restricted diffusion secondary to cytotoxic and/or intramyelinic edema. These disorders include ischemia, infection, noninfectious demyelinating diseases, genetic mutations affecting metabolism, acquired metabolic disorders, toxic or drug exposures, neoplasms and tumorlike lesions, radiation treatment, trauma, and denervation.