The clinical success of medical devices is ultimately determined by their biocompatibility. Medical devices have to possess all the required characteristics to ensure clinically acceptable biocompatibility. The de…nition of biocompatibility that is most commonly used these days was formulated by D. Williams some years ago as “The ability of a material to perform with an appropriate response in a speci…c application” [1,2]. This de…nition takes into account that a biomaterial does not only have a passive, supportive, or mechanical function but also has an important role in guiding the host response toward the biomedical implant. This means that the biofunctionality of the implant is an intricate characteristic of the device. It is unavoidable that the body reacts to a newly implanted material with a wide range of defense mechanisms. This response is known as the foreign body response [3]. Over the past decades, different strategies to obtain acceptable host response to medical implants have been applied. These range from trying to achieve perfect inertness to implants with highly bioactive or biofunctionalized surfaces to actively induce a desired host-tissue response. There has been success with many biomedical implants, but most of these do not carry bioactivity in or on the device [4]. Clinical practice demonstrates that design of a truly bioactive implant is dif…cult since the exact hostresponse cannot be predicted. The way in which the tissue will respond to the invading foreign material is dependent on many factors and differs between patients signi…cantly. After a while, a fragile dynamic equilibrium is reached between the materials and the surrounding tissue. The implanted materials will perform well until a slight change in one of the interaction parameters, causing a series of events that will lead to the disturbance of the delicate equilibrium and may result in failure of the device. This also means that the variation between the treated patients makes prediction of the performance of a biomaterial virtually impossible. For instance when considering hip replacement, the quality of the bone in which the stem and cup are …xed are of critical importance for the clinical outcome of the device. One can easily imagine that patients suffering from osteoporosis may have a poorer clinical outcome than patients who do not suffer from this bone disease [5]. Another example that demonstrates the effect of, on …rst sight, minor details is the performance of mechanical heart valves. The thrombotic complications of metallic and polymeric parts of this medical device are suppressed by anticoagulants and/or antiplatelet drugs. A simple visit to the dentist, e.g., to remove a tooth, will require the reduction of this anticoagulant therapy for a short while. The risk of thrombosis will increase in this short period, although the materials do not change. There is a signi…cant change in one of the parameters that determines the delicate equilibrium between the blood and the blood contacting surfaces of the mechanical valve. Also for patients that have received a coronary stent, patient compliance concerning the anticoagulation therapy has been shown to be the cause of late-stent thrombosis, leading to failure of the device and in worst cases death [6,7]. These examples show that reduction in the number of parameters determining the tissue-implant equilibrium can be bene…cial for the clinical success of the medical device. In some cases this means that biofunctionalization of biomaterial surfaces is a viable strategy to increase the long-term performance. In the cases of the stents and heart valves, a coating that would inhibit/suppress surface-induced blood coagulation will not only decrease side effects, like prolonged bleeding, but also would prevent failure of the device because of poor patient compliance concerning the anticoagulation therapy. Therefore, the introduction of bioactivity in theory is a useful characteristic of any biomaterial. We should however not forget that next to the practical problems concerning bioactive biomaterials (sterilization, costs, limited shelf life, storage conditions, etc.), the intended biological response to the implant may differ considerably between patients. Even after thorough testing, the intended functionality of the implant may vary because of the subtle differences of the tissue environment that are encountered in different patients.