Joint replacements have considerably improved the quality of life of patients with joints damaged by disease or trauma. However, problems associated with wear particles generated due to the relative motion between the components of the bearing are still present and can lead to the eventual failure of the implant. The biological response to wear debris is directly related to prosthesis longevity. The identification of the mechanisms by which cells respond to wear debris and how particles distribute around the human body may provide valuable information for the long term success of artificial joints.During the last few decades, orthopaedic research has been focused on predicting the in vivo performance of joint replacements. However, the exact interrelationship between material physicochemical properties and inflammatory response is not fully understood to date. Laboratory wear simulators provide an accurate prediction of implant wear performance. However, particles generated from such wear simulators require validation to compare them with particles extracted from peri-implant tissues. The present work focuses initially on the advantages and disadvantages of the different bearing combinations (hard-on-soft and hard-on-hard bearings). In addition, the similarities between particles observed in vivo and those generated in vitro to predict the cellular response to wear debris is discussed. Finally, the biological effects of the degradation products generated by wear and corrosion are described.