Since the 1960s, efforts have been made to develop new technologies to eliminate the risk of thrombosis in medical devices that come into contact with blood. Preventing thrombosis resulting from the contact of a medical device, such as an implant, with blood is a challenge due to the high mortality rate of patients and the high cost of medical care. To this end, various types of biomaterials coated with polymer-drug layers are being designed to reduce their thrombogenicity and improve their hemocompatibility. This review presents the latest developments in the use of polymer-drug systems to produce anti-thrombogenic surfaces in medical devices in contact with blood, such as stents, catheters, blood pumps, heart valves, artificial lungs, blood vessels, blood oxygenators, and various types of tubing (such as for hemodialysis) as well as microfluidic devices. This paper presents research directions and potential clinical applications, emphasizing the importance of continued progress and innovation in the field.