Strategies to design vascular grafts with improved biocompatibility must be based on a thorough understanding of the molecular mechanisms that drive the host response to foreign bodies. Thus, the implantation of synthetic vascular grafts perturbs the homeostatic balance and triggers thrombosis and inflammation, which can lead to thrombotic occlusion, fibrous encapsulation, and clacification. Surface modifications are aimed at avoiding these complications, while recapitulating the mechanical properties of the native vessels. Synthetic blood vessels must be sufficiently elastic and compliant to prevent mechanical mismatch and resistance to long-term fatigue. In addition, they must have sufficient suture retention strength to tolerate the hydrodynamic and mechanical forces at the sites of anastomosis. Expanded polytetrafluoroethylene (ePTFE) and polyethylene terephthalate vascular grafts are those most widely used, but at least 50% fail within 10 years mainly because they lack a functional endothelium that resists thrombosis. Surface modifications can reduce thrombogenicity, enhance patency, and promote tissue regeneration. Reducing thrombogenicity through surface modification also can eliminate the need for antithrombotic drugs, thereby reducing the risk of hemorrhagic complications. This review focuses on biomaterial surface modification techniques in current use in vascular tissue engineering.