Introduction: Stereotactic body radiation therapy (SBRT) uses advanced technology to deliver a potent ablative dose to deep-seated tumors in the lung, liver, spine, pancreas, kidney, and prostate. Methods: SBRT involves constructing very compact high-dose volumes in and about the tumor. Tumor position must be accurately assessed throughout treatment, especially for tumors that move with respiration. Sophisticated image guidance and related treatment delivery technologies have developed to account for such motion and efficiently deliver high daily dose. All this serves to allow the delivery of ablative dose fractionation to the target capable of both disrupting tumor mitosis and cellular function. Results: Prospective phase I dose-escalation trials have been carried out to reach potent tumoricidal dose levels capable of eradicating tumors with high likelihood. These studies indicate a clear dose-response relationship for tumor control with escalating dose of SBRT. Prospective phase II studies have been reported from several continents consistently showing very high levels of local tumor control. Although late toxicity requires further careful assessment, acute and subacute toxicities are generally acceptable. Patterns of toxicity, both clinical and radiographic, are distinct from those observed with conventionally fractionated radiotherapy as a result of the unique biologic response to ablative fractionation. Conclusion: Prospective trials using SBRT have confirmed the efficacy of treatment in a variety of patient populations. Although mechanisms of ablative-dose injury remain elusive, ongoing prospective trials offer the hope of finding the ideal application for SBRT in the treatment arsenal.