The most common cause of failure of total hip and other arthroplasties is aseptic loosening of the prosthesis. Substantial evidence suggests that the adverse tissue response to prosthesis wear particles is an important contributor to bone loss around implants. The results may be an increased risk of loosening and severe bone loss, which makes revision surgery more difficult. Studies in humans have demonstrated that the appearances of the periprosthetic tissues are related to the type, number, and size of wear particles. The appearance and tissue response around any given prosthesis is related to the balance among the rate of production of wear particles, the ability of the tissues to deal with the particles, and the rate of clearance of the particles from the joint. Prosthesis wear particles may be produced by wear at the articulating surface, particularly if there is three-body wear, by abrasion due to movement at the prosthesis-bone interface of uncemented prostheses, by abrasion at the prosthesis-cement and cement-bone interfaces of cemented prostheses, or at any articulation of the components of modular prostheses. Future in vivo and in vitro studies of the effects of wear particles should focus on quantitative measurement of the effects of particles and on the use of particles of comparable size and in concentrations similar to those found in the tissues surrounding failed prostheses.