Radioembolization (RE) is a relatively novel treatment modality for primary and secondary hepatic malignancies. Microspheres embedded with a β-emitting radioisotope are injected into the hepatic artery, resulting in microsphere deposition in the tumor arterioles and normal portal triads. Microsphere deposition in nontumorous parenchyma can result in radiation-induced liver injury, with lethal RE-induced liver disease (REILD) at the outer end of the spectrum. The primary aim of this study was to evaluate RE-related hepatotoxicity and present an overview of the currently applied definitions and clinically relevant characteristics of REILD. A systematic literature search on REILD was performed. Studies after the introduction of the term REILD (2008) were screened for definitions of REILD. Hepatotoxicity and applied definitions of REILD were compared. Liver biochemistry test abnormalities occur in up to 100% of patients after RE, mostly self-limiting. The incidence of symptomatic REILD varied between 0 and 31%, although in most reports, the incidence was 0-8%, with a lethal outcome in 0-5%. With the exception of bilirubin, the presentation of hepatotoxicity and REILD was similar for cirrhotic and noncirrhotic patients. No uniform definition of REILD was established in the current literature. Here, we propose a unifying definition and grading system for REILD. RE-related hepatotoxicity is a common phenomenon; symptomatic REILD, however, is rare. Currently, reporting of REILD is highly variable, precluding reliable comparison between studies, identification of risk factors, and treatment developments.