Abstract An “abscopal” effect occurs when localized irradiation perturbs the organism as a whole, with consequences that can be either beneficial or detrimental. Mechanistic explanations of this effect are challenging. From the oncologist’s perspective, the term refers to distant tumor regression after localized irradiation. On the other hand, from a biologist’s point of view, abscopal effects include induction of genomic instability, cell death, and oncogenic transformation in normal tissues. This conceptual dichotomy is explored in this review, with a focus on clinically documented cases of anti-tumor abscopal effects and abscopal effects in normal tissues. This review also outlines several suggested mechanisms for abscopal effects.