Balloon angioplasty revolutionized coronary revascularization; however, elastic recoil and restenosis caused by cellular proliferation are major drawbacks of angioplasty. Intracoronary stenting, which could tackle dissections and eliminate elastic recoil, became the next mode of intervention but was limited by stent thrombosis and increased neointimal hyperplasia, leading to in-stent restenosis. Drug-eluting stents significantly attenuate the cellularity and reduce the need for repeat revascularization; however, late stent thrombosis, dependency on prolonged dual antiplatelet therapy, and continued restenosis led to a quest for new treatment modalities. In recent years, drug-eluting balloons (DEB) have emerged as a potential alternative to combat restenosis. Paclitaxel was identified as the primary drug for DEB because of its rapid uptake and prolonged retention. DEB technology demonstrated safety and efficacy in preclinical and in randomized clinical trials for patients with in-stent restenosis. Further studies for de novo lesions in small vessels, for lesions in the superficial femoral artery, and those for below the knee signal its safety and efficacy for broader indications. This review will discuss the rationale, concept, and available DEB technologies, along with preclinical and clinical data, to support the DEB as a new technology for endovascular intervention. It will also assess the potential of the balloon to become the “comeback kid” of percutaneous coronary intervention in the form of DEB. The use of percutaneous balloon angioplasty to recanalize narrowed coronary arteries and endovascular vessels revolutionized revascularization.1 Balloon angioplasty, however, was associated with subintimal dissection, abrupt vessel closure, and restenosis. Stents tackle dissection, eliminate the elastic recoil and late negative vessel remodeling,2 but increase inflammation, thereby leading to more intimal hyperplasia resulting in in-stent restenosis (ISR).3 The major limitation of stents is stent thrombosis, which is controlled with antiplatelet therapy. Drug-eluting stents (DES) are another breakthrough in stent technology because of their ability to …