While conventional treatment relies on protracted courses of therapy using relatively small dose-per-fraction sizes of 1.8–2 Gy, there is substantial evidence gathered over decades that this may not be the optimal approach for all targetable disease. Stereotactic ablative body radiosurgery (SABR) or stereotactic body radiation therapy (SBRT) is a technique which uses precise targeting to deliver high doses of radiation capable of ablating tumors directly. In this review, we will discuss the justification for and techniques used to deliver ablative doses to improve treatment outcomes, interactions with biological and immunologic therapy, and special procedures to spare normal tissue, which have facilitated the expanding role for these techniques in the management of a wide range of malignant histologies and disease states.