Prosthetic devices that come into contact with blood ultimately fail secondary to thrombus formation. This limits the utility of a variety of materials used to surgically treat cardiovascular disease, including vascular grafts and stents, as well as sensors and catheters placed within the circulatory system. Moreover, systemic anticoagulation that is used to prevent malfunction of these devices has potential for serious complications. It is known that nitric oxide (NO) produced via the endothelium imparts thromboresistant properties to native blood vessels. Thus, if NO were delivered locally to the site of the prosthetic material, it has the potential to halt thrombus formation while limiting life-threatening side effects. This review serves to examine the variety of NO-releasing materials that have been created with the two different classes of NO donors, the diazeniumdiolates and S-nitrosothiols, and the clinical applications of these prosthetics for potential future use.