Diffusion-weighted (DW) magnetic resonance (MR) imaging is emerging as a powerful clinical tool for directing the care of patients with cancer. Whole-body DW imaging is almost at the stage where it can enter widespread clinical investigations, because the technology is stable and protocols can be implemented for the majority of modern MR imaging systems. There is a continued need for further improvements in data acquisition and analysis and in display technologies. Priority areas for clinical research include clarification of histologic relationships between tissues of interest and DW MR imaging biomarkers at diagnosis and during therapy response. Because whole-body DW imaging excels at bone marrow assessments at diagnosis and for therapy response, it can potentially address a number of unmet clinical and pharmaceutical requirements. There are compelling needs to document and understand how common and novel treatments affect whole-body DW imaging results and to establish response criteria that can be tested in prospective clinical studies that incorporate measures of patient benefit. © RSNA 2011.