Percutaneous coronary intervention (PCI) represents a technical advance in the treatment of coronary artery disease. However, it is not without risks both during and after the procedure. In-stent restenosis (ISR) is the most common complication following PCI. Individuals who experience angina associated with ISR often fail to recognize its seriousness and, therefore, do not respond appropriately to the situation. Individuals with ISR are vulnerable to the consequences of angina, including increased morbidity and mortality, as well as a decreased health-related quality of life. In this article, the authors review the risks for developing ISR, the pathophysiology of angina related to ISR, and the challenges that face patients who develop recurrent angina post-PCI. Cardiovascular nurses play a critical role in the clinical management and education of patients following PCI. The provision of post-PCI follow-up care is key to identifying, managing, and supporting patients with recurrent angina.