Professor Lars Leksell selected Cobalt-60 as the ideal photon radiation source for radiosurgery after investigating protons and cross fired photons form early generation linear accelerator [1,2]. The first Gamma Knife (179 Co-60 sources) created a discoid-shaped lesion suitable for movement disorder and intractable pain surgery. Clinical experience with the Gamma Knife began in 1967 with the treatment of a patient with craniopharyngioma. Lunsford and colleagues introduced the first clinical 201-source Gamma Knife unit (model U) to North America (the fifth gamma unit worldwide) which was installed in August 1987 at University of Pittsburgh Medical Center. To eliminate challenging reloading issues associated with model U design, the Gamma Knife was redesigned with sources arranged in a circular (O-ring) configuration. The second generation unit (Model B) was installed at the University of Pittsburgh in 1996. Later the robotic automated positioning system (APS) transformed this unit into the third generation technology model C in March 2000. In January 2005 the fourth generation Leksell Gamma Knife model 4-C was installed. The model 4-C was equipped with hardware and software enhancements designed to improve workflow and provide integrated imaging capabilities, especially image fusion.