This report describes the technique and initial experience using cone beam CT (CBCT) for localization of treatment targets in patients undergoing stereotactic body radiation therapy (SBRT). Patients selected for SBRT underwent 3-D or 4-D CT scans in a customized immobilization cradle. GTV, CTV, ITV, and PTV were defined. Intensity-modulated radiation beams, multiple 3-D conformal beams, or dynamic conformal arcs were delivered using a Varian 21EX with 120-leaf MLC. CBCT images were obtained prior to each fraction, and registered to the planning CT by using soft tissue and bony structures to assure accurate isocenter localization. Patients were repositioned for treatment based on the CBCT images. Radiographic images (kV, MV, or CBCT) were taken before and after beam delivery to further assess set-up accuracy. Ten patients with lung, liver, and spine lesions received 29 fractions of treatment using this technique. The prescription doses ranged 1250 approximately 6000 cGy in 1 approximately 5 fractions. Compared to traditional 2-D matching using bony structures, CBCT corrects target deviation from 1 mm to 15 mm, with an average of 5 mm. Comparison of pre-treatment to post-treatment radiographic images demonstrated an average 2 mm deviation (ranging from 0-4 mm). Improved immobilization may enhance positioning accuracy. Typical total "in-room" times for the patients are approximately 1 hour. CBCT-guided SBRT is feasible and enhances setup accuracy using 3-D anatomical information.