Tomosynthesis is a decades-old technique for section imaging that has seen a recent upsurge in interest due to its promise to provide three-dimensional information at lower dose and potentially lower cost than CT in certain clinical imaging situations. This renewed interest in tomosynthesis began in the late 1990s as a new generation of flat-panel detectors became available; these detectors were the one missing piece of the picture that had kept tomosynthesis from enjoying significant utilization earlier. In the past decade, tomosynthesis imaging has been investigated in a variety of clinical imaging situations, but the two most prominent have been in breast and chest imaging. Tomosynthesis has the potential to substantially change the way in which breast cancer and pulmonary nodules are detected and managed. Commercial tomosynthesis devices are now available or on the horizon. Many of the remaining research activities with tomosynthesis will be translational in nature and will involve physicist and clinician alike. This overview article provides a forward-looking assessment of the translational questions facing tomosynthesis imaging and anticipates some of the likely research and clinical activities in the next five years.