Diffusion-weighted magnetic resonance (MR) imaging (DWI) is increasingly applied to evaluate tumors in the abdomen and pelvis. However, DWI is susceptible to a variety of artifacts that arise from motion, use of strong gradient pulses, and echo-planar imaging technique. We discuss practical issues to help radiologists optimize the use of DWI to evaluate tumors in the body, including breath-hold DWI, multiple-acquisition non-breath-hold DWI, and diffusion-weighted whole-body imaging with background body signal suppression (DWIBS). Considerations of meticulous technique, sequence optimization, and quality assurance are emphasized for consistent acquisition of high quality images. We illustrate the potential use of these techniques to detect and characterize tumors and to monitor treatment effects.