Restenosis (also known as ISR) is defined as recurrence of coronary artery narrowing after percutaneous coronary intervention (PCI). It is considered the most significant problem in coronary interventional treatment. In this chapter definition, classification, mechanism of ISR along with clinical approach and management are discussed in detail. The management of ISR includes role of intravascular imaging, balloon angioplasty, cutting and scoring balloon angioplasty, vascular brachytherapy, repeat stenting with bare-metal stents, repeat stenting with drug-eluting stents and drug-coated balloon angioplasty. Evidence stemming from controlled clinical studies suggests that among currently available therapeutic modalities, DES and DCB provide the best clinical and angiographic results in patients with ISR.