Improving the performance of blood-contacting medical implants is a global health necessity aimed at reducing mortality and morbidity in patients with cardiovascular diseases. Surface modification of the biomaterials from which the vascular grafts are constructed has been used to reduce the risk of complications such as thrombosis and infection. Herein with a focus on vascular tissue engineering, we provided an overview of (a) fundamental hemodynamic considerations for blood-contacting biomaterials, (b) surface modification strategies to attenuate nonspecific adhesion of proteins, improve hemocompatibility, and induce the formation of a confluent endothelial lining, and (c) the guidelines for the clinical development of surface modified biomaterials.