OBJECT: Photon energy deposition from gamma or photon sources follows the law of exponential decay. Consequently, energy is deposited over the entire path of the radiation beam, resulting in dose distribution before and after the target is reached. In contrast, the physical properties of protons are such that energy deposition occurs with no exit dose beyond the target volume. Therefore, relative to photons, proton beams represent a superior platform for the administration of radiosurgery. METHODS: In this review, the authors will discuss the fundamental principles underlying photon- and proton-based stereotactic radiosurgery (SRS). The clinical efficacy of proton-based SRS in the treatment of arteriovenous malformations, vestibular schwannomas, and pituitary adenomas is reviewed. RESULTS: Direct comparisons of clinical results attained using photon- and proton-based SRS are confounded by a bias toward reserving proton beams for the treatment of larger and more complex lesions. Despite this bias, the clinical outcomes for proton-based SRS have been excellent and have been at least comparable to those for photon-based treatments. CONCLUSIONS: The physical properties of proton radiation offer superior conformality in dose distribution relative to photon irradiation. This advantage becomes more apparent as the lesion size increases and will probably be magnified with the development of intensity-modulated proton techniques.