Drug-coated balloons (DCBs) have become an established therapy for the treatment of above-the-knee peripheral artery disease. The paclitaxel DCB has shown clinical benefit in terms of patency and freedom from re-intervention in multiple randomised trials. However, a recent meta-analysis has suggested an association between mortality and the use of paclitaxel-coated devices. Sirolimus is another potential choice of anti-proliferative agent for use in DCBs because of its wider therapeutic index and lower risk for dose-dependent toxicity. More recently, encapsulating sirolimus in micro-reservoirs or polymers has facilitated the development of effective sirolimus DCBs, some of which are available in Europe and Asia. In this review, the authors focus on paclitaxel and sirolimus DCB technologies from the standpoint of drug characteristics and clinical trials.