The range of clinical applications for stereotactic body radiation therapy (SBRT) continues to expand based on clinical outcomes data from prospective trials and carefully analyzed institutional experiences. As a result of this strong scientific foundation, there has been burgeoning implementation of SBRT and other forms of hypofractionated radiation therapy in the practice of radiation oncology worldwide. In spite of the clinical successes achieved thus far - or, perhaps, because of them - fundamental questions about SBRT remain and have come into greater focus. Where and when is SBRT optimally integrated into the range of evolving modern multidisciplinary cancer treatment programs? What scientific insights (biological, technical and medical) might lead to further improvements in the efficacy of SBRT? What efficiencies are needed to achieve greater availability of SBRT? These and many other questions, fueled by the clinical accomplishments of SBRT to date, provide compelling directions for further exploration in scientific and clinical studies and further contributes to discoveries already transforming the practice of radiation oncology.