Although drug-eluting stents (DES) have markedly reduced the incidence of stent restenosis (SR), the increased number and complexity of percutaneous coronary interventions performed worldwide explain the sustained prevalence of SR. Intracoronary imaging techniques remain essential tools to unravel the underlying mechanical causes potentially leading to SR. Current clinical trial data suggest that DES are the most effective therapy for the management of both bare-metal stents SR and DES-SR. In this setting, however, drug-eluting balloons represent a valid therapeutic alternative with the attractive advantage of not requiring the implantation of an additional metallic layer. In this review, we will discuss trial data on the historical evolution and the evidence supporting currently available therapeutic modalities for patients with bare-metal stents SR or DES-SR.