Whole-body diffusion-weighted (DW) imaging is a recent development. The image contrast is based on differences in mobility of water between tissues and reflects tissue cellularity and integrity of cell membranes. The tissue water diffusivity is quantified by the apparent diffusion coefficient. By performing imaging at multiple imaging stations, whole-body DW imaging has been applied to improve tumor staging, disease characterization, as well as for the assessment of treatment response. Information from DW imaging studies could be combined with those using PET imaging tracers to further refine and improve the assessment of patients with cancer.