In-stent restenosis (ISR) after non-coronary interventions is becoming an increasing clinical and technical problem in daily practice due to the more liberal use of stents particularly in femoro-popliteal and infra-popliteal interventions. Whereas in the coronaries the role of drug eluting stents (DES) in the treatment of ISR is already well defined, very limited data exist about the use of DES in the treatment of ISR in non-coronary arteries. So far little data is published on the potential role of DES in in-stent restenosis except in renal artery interventions. The concept of DES in femoro-popliteal lesions even excluding ISR so far failed for sirolimus and everolimus eluting self-expanding stents. In infra-popliteal lesions promising single centre reports have already been published. Own single center reports showed favorable patency rates for the treatment of renal artery ISR. So far, only one study - the Zilver(R) PTX(R) single arm study - investigates in a subcohort of 120 of 818 lesions the outcome of a paclitaxel eluting DES in treating ISR in femoro-popliteal arteries. The Zilver(R) PTX(R) stent consists of a self-expanding nitinol stent platform with a polymer free paclitaxel coating with a dose density of 3 mg/mm2. In an interim analysis the freedom from target lesion revascularization is 78% after one year. Even if not yet having data for primary and secondary patency available, these results compare favorably with alternative treatment options such as plain balloon angioplasty and cutting balloon angioplasty or even directional atherectomy. No data have been published or presented yet about the treatment of infra-popliteal ISR. Randomized comparative trials comparing dedicated DES with standard interventional techniques such as plain old balloon angioplasty for the treatment of ISR in femoro-popliteal and infra-popliteal ISR are mandatory.