Endothelial cell injury is considered to play a critical role for development and progression of atherosclerosis as well as for complications after percutaneous coronary artery interventions in patients with coronary disease. Through the course of human life, the endothelium is constantly replaced and exposure to endothelial cell damaging stimuli, such as cardiovascular risk factors, requires a substantially faster repair and replacement response in order to maintain endothelial integrity and function. Moreover, after coronary interventions, the induced vascular injury requires a fast and efficient re-endothelialization in order to prevent thrombotic events. The promotion of endothelial repair and re-endothelialization responses in patients with cardiovascular disease is therefore a therapeutic target of high interest. In this review we will critically summarize novel insights into the vascular repair process, as well as the tightly linked mechanisms of adverse vascular remodeling. We will address the roles of resident vascular cell types, as well as circulating mononuclear cell populations, microvesicles and soluble mediators for the vascular repair response. A better understanding of the mechanisms limiting vascular repair in patients with cardiovascular disease may provide novel opportunities for therapeutic interventions aiming to promote the maintenance of vascular integrity.