Intracoronary brachytherapy has been developed as an adjunctive treatment strategy for prevention and treatment of restenosis. Two technologies, one employing radioactive stents, the other catheter-based radiation systems (beta or gamma), have been tested in several animal and human studies in both de novo and restenotic coronary lesions. In particular, intravascular ultrasound imaging studies have given great insights into the mechanisms of action of intracoronary brachytherapy and its complications. Negative results from clinical trials performed in patients with de novo coronary lesions and the encouraging results obtained with drug-eluting stents have lead intracoronary brachytherapy to be abandoned in this clinical context, while it still remains the best therapeutic tool for the treatment of patients with in-stent restenosis. In this manuscript, principles of radiation therapy, results of clinical trials, current clinical practice, and future perspectives of intracoronary brachytherapy are summarized.