Stereotactic body radiation therapy (SBRT) is a potent noninvasive means of administering high radiation doses to demarcated tumor deposits in extracranial locations. The treatments use image guidance and related advanced treatment delivery technologies for the purpose of escalating the radiation dose to the tumor, while sharply minimizing the radiation doses to surrounding normal tissues. The local tumor control outcomes for SBRT have been higher than any previously published for the radiotherapy of frequently occurring carcinomas. In addition, the pattern, timing and severity of the toxicities have been very different than from those seen with conventional radiotherapy. These issues pose challenges to our understanding of the radiobiological mechanisms and the optimal uses of SBRT. In this review, the clinical characteristics and outcomes of SBRT are presented in the context of their possible underlying mechanisms. While some of these considerations remain theoretical, they may outline at least qualitative understandings of the observed clinical effects, and motivate continuing research into the effects of SBRT that guide its most effective use in the clinic.