PurposeThe purpose of this study was to review the role of radioactive microparticles (1–100 μm) for the treatment of solid tumors and provide a comprehensive overview of the feasibility, safety, and efficacy.MethodsA systematic search was performed in MEDLINE, EMBASE, and The Cochrane Library (January 2017) by combining synonyms for the determinants “tumor,” “injection,” and “radionuclide.” Data on injection technique, toxicity, tumor response, and survival were collected.ResultsThe search yielded 7271 studies, and 37 were included for analysis. Twelve studies were performed in human patients and 25 animal studies. The studies were heterogeneous in patient population, tumors, follow-up time, and treatment characteristics. The direct intratumoral injection of radioactive microparticles resulted in a response rate of 71% in a variety of tumors and uncomplicated procedures with high cumulative doses of >19,000 Gy were reported.ConclusionThe large variety of particles, techniques, and treated tumors in the studies provided an important insight into issues concerning efficacy, safety, particle and isotope choice, and other concepts for future research. Animal studies showed efficacy and a dose response. Most studies in humans concluded that intratumoral treatment with radioactive beta-emitting microparticles is relatively safe and effective. Conflicting evidence about safety and efficacy might be explained by the considerable variation in the treatment characteristics. Larger particles had a better retention which resulted in higher anti-tumor effect. Leakage seems to follow the path of least resistance depending on anatomical structures. Subsequently, a grid-like injection procedure with small volume depots is advised over a single large infusion. Controlled image-guided treatment is necessary because inadequate local delivery and inhomogeneous dose distribution result in reduced treatment efficacy and in potential complications.