CABG surgery is an effective way to improve symptoms and prognosis in patients with advanced coronary atherosclerotic disease. Despite multiple improvements in surgical technique and patient treatment, graft failure after CABG surgery occurs in a time-dependent fashion, particularly in the second decade after the intervention, in a substantial number of patients because of atherosclerotic progression and saphenous-vein graft (SVG) disease. Until 2010, repeat revascularization by either percutaneous coronary intervention (PCI) or surgical techniques was performed in these high-risk patients in the absence of specific recommendations in clinical practice guidelines, and within a culture of inadequate communication between cardiac surgeons and interventional cardiologists. Indeed, some of the specific technologies developed to reduce procedural risk, such as embolic protection devices for SVG interventions, are largely underused. Additionally, the implementation of secondary prevention, which reduces the need for reintervention in these patients, is still suboptimal. In this Review, graft failure after CABG surgery is examined as a clinical problem from the perspective of holistic patient management. Issues such as the substrate and epidemiology of graft failure, the choice of revascularization modality, the specific problems inherent in repeat CABG surgery and PCI, and the importance of secondary prevention are discussed.