(18)F-FDG PET is an established functional imaging modality for the evaluation of human disease. Diffusion-weighted MRI (DWI) is another rapidly evolving functional imaging modality that can be used to evaluate oncologic and nononcologic lesions throughout the body. The information provided by (18)F-FDG PET and DWI can be complementary, because the 2 methods are based on completely different biophysical underpinnings. This article will describe the basic principles, clinical applications, and limitations of DWI. In addition, the available evidence that correlates and compares (18)F-FDG PET and DWI will be reviewed.