The basis for interest in proton beams by clinical radiation oncologists lies in reduction in treatment volume. The yields from employing a smaller treatment volume are the increase of tumor control probability and the reduction of normal tissues complication probability. The clinical use of proton therapy began in 1954 at Uppsala University in Sweden and in 1961 at Harvard Cyclotron Laboratory in Boston, USA. So far, the total number of worldwide patients treated by protons is about 20,000. In this paper attention will be given to the treatment of patients at the Massachusetts General Hospital-Massachusetts Eye and Ear Infirmary-Harvard Cyclotron Laboratory, and at the Loma Linda University Medical Center. In particular, a review of the literature about the techniques and the results of treatment of skull base and cervical spine chordoma and low-grade chondrosarcoma, skull base meningioma, pituitary tumors, paranasal sinus carcinoma, glioblastoma multiforme, artero-venous malformations, uveal melanoma, macular degeneration, retinoblastoma, thoracic spine-sacrum tumors, and prostate carcinoma is presented. In order to verify and improve the clinical results, the conduct of prospective trials on an inter-institutional basis is essential. To facilitate the conduct of such studies the US National Cancer Institute and the American College of Radiology have established the Proton Therapy Oncology Group (PROG). Several phase III and some phase I-II trials are active at the Massachusetts General Hospital, Harvard Cyclotron Laboratory, and at the Loma Linda University Medical Center.