Radiotherapy (RT) has continuously evolved through last century as one of the pillars of cancer treatment [1]. Immediately after the discovery of X-rays by Wilhelm Röentgen in 1895, radiation was experimentally used in the treatment of various tumors (Fig. 17.1) [2]. Since then, the indications of RT have broadened, and dose-fractionation regimes in tumors were established. Approximately at the same period, Ernst Rutherford discovered protons in 1917 (Fig. 17.2) [3]. In 1930, Ernest O. Lawrence and his associates invented the cyclotron to accelerate proton to the energy high enough for cancer treatment applications (Fig. 17.3) [4]. He won the 1939 Nobel Prize for physics for this work. In 1931, he founded the Radiation Laboratory, later called the Lawrence Berkeley National Accelerator Laboratory (LBNL), where the first synchrocyclotron was developed a decade later and was used to accelerate heavy ions as well (Fig. 17.4) [5].