In 2001 the CyberKnife® System received FDA clearance for treatment of tumors anywhere in the body that radiation was indicated. Since then CyberKnife users have developed and continue to develop protocols for treating tumors in the brain, spine, lungs, liver, pancreas, kidney, and prostate. In these pages we describe these applications, and how CyberKnife users have approached them. As these clinical developments evolve so will our technology; the evolution of the technology will be driven clinically so that patients continue to receive the best, least invasive radiosurgical treatment.