In-stent restenosis (ISR) remains the most common cause of stent failure after percutaneous coronary intervention (PCI). Recent data suggest that ISR-PCI accounts for 5-10% of all PCI procedures performed in current clinical practice. This State-of-the-Art review will primarily focus on the management of ISR but will begin by briefly discussing diagnosis and classification. We then move on to detail the evidence base underpinning the various therapeutic strategies for ISR before finishing with a proposed ISR management algorithm based on current scientific data.