Despite technical advances in percutaneous coronary intervention (PCI) and new iterations of drug-eluting stents (DES), complications still occur, including stent thrombosis and in-stent restenosis (ISR). Drug-coated balloons (DCBs) provide a promising option for the treatment of coronary lesions – particularly when DES are undesirable or contraindicated – allowing for PCI without the implantation of metallic devices, thus adhering to the ‘leave nothing behind’ principle. A comprehensive literature search has been performed on PubMed, Web of Science and Cochrane, up to November 2024, with no significant restrictions. This article provides an overview of available DCB and summarizes the evidence supporting their use in different settings, including ISR, small-vessel disease, de novo large-vessel disease, and bifurcations. Trials of DCB are heterogeneous with respect to population, sample size, follow-up, anatomical pattern, and device used. Furthermore, they usually have limited statistical power for clinical endpoints. Based on current knowledge, DES may be preferrable for DES-ISR, de novo lesions in large vessels and for the treatment of the main branch in true bifurcations, with DCB approved for small-vessel disease and selected ISR lesions. Ongoing trials are expected to provide definitive insights into the efficacy and safety of DCB in different scenarios.