Drug coated balloons (DCBs) are currently indicated in guidelines as a first choice option in the management of instant restenosis, whereas their use in de novo lesions is still debated. The concerns raised after the contrasting results of the initial trials with DCBs in de novo lesions have been more recently overcome by a larger amount of data confirming their safety and effectiveness as compared to drug-eluting stents (DES), with potentially greater benefits being achieved, especially in particular anatomical settings, as in very small or large vessels and bifurcations, but also in selected subsets of higher-risk patients, where a ‘leave nothing behind’ strategy could offer a reduction of the inflammatory stimulus and thrombotic risk. The present review aims at providing an overview of current available DCB devices and their indications of use based on the results of data achieved so far.