In-stent restenosis (ISR) remains a potential complication after percutaneous coronary intervention, even in the era of drug-eluting stents, and its treatment remains suboptimal. Neoatherosclerosis is an important component of the pathology of ISR and is accelerated in drug-eluting stents compared with bare-metal stents. Coronary angiography is the gold standard for evaluating the morphology of ISR, although computed tomography angiography is emerging as an alternative noninvasive modality to evaluate the presence of ISR. Drug-coated balloons and stent reimplantation are the current mainstays of treatment for ISR, and the choice of treatment should be based on clinical background and lesion morphology.