In-stent restenosis (ISR) is a challenging clinical problem after intervention therapy of femoropopliteal (FP) arterial occlusive disease. Femoropopliteal artery in-stent restenosis (FP-ISR) rates after primary stent implantation are relatively high, and repeat FP-ISR often requires multiple additional interventions. Previous studies mainly focused on balloon angioplasty, bypass surgery, stent-graft, drug-coated balloon, and debulking therapies. However, the optimal approach remains controversial. Recently, the treatment trend has shifted to a combination of two or more methods. Among them, the combination therapy based on Rotarex atherectomy plus debulking has become a new choice for FP-ISR. Here, the authors analyze the safety and efficacy of Rotarex combination therapy used for FP-ISR and also discuss the future prospects.