Maintenance of vascular integrity is essential for the prevention of vascular disease and for recovery following cardiovascular, cerebrovascular and peripheral vascular events including limb ischemia, heart attack and stroke. Endothelial stem/progenitor cells have recently gained considerable interest due to their potential use in stem cell therapies to mediate revascularization after ischemic injury. Therefore, there is an urgent need to understand fundamental mechanisms regulating vascular repair in specific cell types to develop new beneficial therapeutic interventions. In this review, we highlight recent studies demonstrating that epigenetic mechanisms (including post-translational modifications of DNA and histones as well as non-coding RNA-mediated processes) play essential roles in the regulation of endo-thelial stem/progenitor cell functions through modifying chromatin structure. Furthermore, we discuss the potential of using small molecules that modulate the activities of epigenetic enzymes to enhance the vascular repair function of endothelial cells and offer insight on potential strategies that may accelerate clinical applications.