The postoperative occlusion of surgical venous or arterial grafts following coronary artery bypass graft (CABG) surgery is a constant and unsolved problem that has a negative impact on clinical outcomes. Maintaining graft patency is essential to achieve desired effects of CABG surgery. Although CABG is common and reliable revascularization procedure, along with percutaneous coronary intervention (PCI), the management of grafts (prevention of graft occlusion) remains one of the biggest challenges in this field. This review will focus on different factors that influence the development of graft occlusion. Initially, historical aspects of CABG and the pathogenesis of graft occlusion will be reviewed, especially emphasizing the role of inflammatory responses and factors associated with venous graft remodeling. The clinical results and conclusions of the CABG database of the Department of Cardiology, University of Debrecen is also discussed in detail. Finally, the potential therapeutic options will be reviewed together with graft occlusions prevention to improve clinical outcomes after CABG procedure.