Proton beam therapy provides the opportunity for more localized delivery of ionizing radiation with the potential for improved normal tissue avoidance to reduce treatment related morbidity and to allow for dose escalation to improve disease control-and survival without increased toxicity. However, a systematic review of published peer-reviewed literature reported previously and updated here is devoid of any clinical data demonstrating benefit in terms of survival, tumor control, or toxicity in comparison with best conventional treatment. for any of the tumors so far treated including skull base and ocular tumors, prostate cancer and childhood malignancies. The current lack of evidence for benefit of protons should provide a stimulus for continued research. Well designed in silico clinical trials using validated normal tissue complication probability-models are important to predict the magnitude of benefit for individual tumor sites but the future use of protons should be guided by clear evidence of benefit demonstrated in well-designed prospective studies, away from commercial influence, and this is likely to require international collaboration. Any complex and expensive technology, including proton therapy, should not be employed on the basis of belief alone and requires testing to avoid inappropriate use of potential detriment to future patients.