The use of saphenous vein grafts (SVGs) in the surgical management of obstructive coronary artery disease remains high despite a growing understanding of their limitations in longevity. In contemporary practice, approximately 95% of patients receive one SVG in addition to a left internal mammary artery (LIMA) graft. The precise patency rates for SVGs vary widely in the literature, with estimates of up to 61% failure rate at greater than 10 years of follow-up. SVGs are known to progressively degenerate over time and, even if they remain patent, demonstrate marked accelerated atherosclerosis. Multiple studies have demonstrated a marked acceleration of atherosclerosis in bypassed native coronary arteries compared to non-bypassed arteries, which predisposes to a high number of native chronic total occlusions (CTOs) and subsequent procedural challenges when managing graft failure. Patients with failing SVGs frequently require revascularisation to previously grafted territories, with estimates of 13% of CABG patients requiring an additional revascularisation procedure within 10 years. Redo CABG confers a significantly higher risk of in-hospital mortality and, as such, percutaneous coronary intervention (PCI) has become the favoured strategy for revascularisation in SVG failure. Percutaneous treatment of a degenerative SVG provides unique challenges secondary to a tendency for frequent superimposed thrombi on critical graft stenoses, friable lesions with marked potential for distal embolization and subsequent no-reflow phenomena, and high rates of peri-procedural myocardial infarction (MI). Furthermore, the rates of restenosis within SVG stents are disproportionately higher than native vessel PCI despite the advances in drug-eluting stent (DES) technology. The alternative to SVG PCI in failed grafts is PCI to the native vessel, ‘replacing’ the grafts and restoring patency within the previously grafted coronary artery, with or without occluding the donor graft. This strategy has additional challenges to de novo coronary artery PCI, however, due to the high burden of complex atherosclerotic lesion morphology, extensive coronary calcification, and the high incidence of CTO. Large patient cohort studies have reported worse short- and long-term outcomes with SVG PCI compared to native vessel PCI. The PROCTOR trial is a large and randomised control trial aimed at assessing the superiority of native vessel PCI versus vein graft PCI in patients with prior CABG awaiting results. This review article will explore the complexities of SVG failure and assess the contemporary evidence in guiding optimum percutaneous interventional strategy.