Fatigue fracture has been identifi ed as one of the major causes of implant failure of medical devices, and it represents a serious limitation for the intended usage of polymer composites for hard and soft tissue applications. This chapter presents an overview on the fatigue behaviour of polymeric composite biomaterials for bone repair and replacement, dental applications, joint replacement, spine surgery, tendons and ligaments augmentation devices and vascular grafts. Some recent advances in testing techniques are outlined and the future development of fatigue-resistant biocomposites is discussed.