Compared to conventional radiotherapy, proton beam therapy provides a superior distribution of radiation dose due to the physical characteristics of protons. Protons administer a uniform dose across the target and then virtually zero deep to the target and lower dose proximal to the target (for non-superficial lesions). The result is a smaller treatment volume, and therefore a lower incidence and frequency of treatment-related morbidity. Moreover, the reduction in treatment volume permits a higher dose to the tumor. This means an improved local control probability and lower normal tissue complication probability. Evidence-based medicine has demonstrated that clinical gains have been realized in the treatment of patient with uveal melanoma, skull-base or spinal sarcoma and prostate cancer. In the future, more extensive prospective studies are required to assess more completely the potential clinical benefit of proton beam therapy in many anatomical sites in children and adults.