BACKGROUND AND PURPOSE: Clinical target volumes of the thorax and abdomen are typically expanded to account for inter- and intrafractional organ motion. Usually, such expansions are based on clinical experience and planar observations of target motion during simulation. More precise, 4-dimensional motion margins for a specific patient may improve dose coverage of mobile targets and yet limit unnecessarily large field expansions. We are studying approaches to targeting moving tumors throughout the entire treatment process, from treatment planning to beam delivery. MATERIAL AND METHODS: Radio-opaque markers were implanted under CT guidance in the liver at the gross tumor periphery. Organ motion during light respiration was volumetrically imaged by 4D Computed Tomography. Marker motion was also acquired by fluoroscopy and compared with 4DCT data. During treatment, daily diagnostic x-ray images were captured at end-exhale and -inhale for patient setup and target localization. RESULTS: Based on the time-resolved CT data, target volumes can be designed to account for respiratory motion during treatment. Motion of the tumor as derived from 4DCT was consistent with fluoroscopic motion analysis. Radiographs acquired in the treatment room enabled millimeter-level patient set-up and assessment of target position relative to bony anatomy. Daily positional variations between bony anatomy and implanted markers were observed. CONCLUSIONS: Image guided therapy, based on 4DCT imaging, fluoroscopic imaging studies, and daily gated diagonstic energy set-up radiographs is being developed to improve beam delivery precision. Monitoring internal target motion throughout the entire treatment process will ensure adequate dose coverage of the target while sparing the maximum healthy tissue.