In vivo degradation of prosthetic implant materials is increasingly recognized as a major factor limiting the durability of total joint arthroplasty. In vivo degradation occurs primarily by means of wear processes that can generate large quantities of particulate debris. This debris can stimulate an adverse local host response leading to periprosthetic bone loss, which can compromise implant fixation and bone stock. The authors review the basic mechanisms of implant degradation and the host response to particulate degradation products, particularly in the context of the pathogenesis of osteolysis. Submicron polyethylene particles (mean size, 0.5 um) are the dominant type of wear particle present in periprosthetic tissues associated with uncemented hip replacements. Polyethylene wear can be minimized by improving the quality of the polyethylene, avoiding use of large-diameter (greater than 28 mm) femoral heads in total hip arthroplasty, and improving the design and fabrication of modular connections, which can be important sources of three-body wear particles. Advances in the understanding of the basic mechanisms of osteolysis are critical to the development of preventive measures that will minimize the clinical impact of this phenomenon.