The use of drug-eluting balloons for treatment of long-segment femoropopliteal artery obstructions has become widespread in recent years. The possibility to deliver a drug into the arterial wall with sustained antiproliferative effects, without leaving behind metal scaffolding, seems very promising. The current generation of drug-eluting balloons differs in the formulation of the drug (usually paclitaxel), technique of coating, and the elution excipients. Results of published randomized trials are reviewed in this report. A new innovative coating technique has been introduced recently. The PRIMUS® coronary drug-eluting balloon and the Legflow® peripheral drug-eluting balloon consist of paclitaxel nanoparticles that are embedded underneath the surface of the balloon as well as inside a new shellolic acid drug-release matrix. Risk for dislodgement of the paclitaxel particles is minimized in the newest generation of drug-eluting balloons. Short-term in vitro and in vivo results of this stable, coated balloon are promising, and large randomized trials have been started recently to gather more long-term and robust clinical data.