This chapter will focus on the biologic responses associated with total hip arthroplasty (THA) failure, which will be subdivided into the topics of bearing surface wear, osteolysis, aseptic loosening, and adverse local tissue reaction or adverse reaction to metal debris. Bearing surface wear, specifically wear of polyethylene, is associated with a macrophage predominated response and can result in significant bone loss. Wear of metal-on-metal implants leads to a lymphocyte predominated response and has been associated with cases of significant bone loss and massive soft-tissue damage. The science of THA failure is essentially the science of component wear, and this science has simultaneously produced a man-made disease akin to malignancy (Harris, Clin Orthop Relat Res 467:28–31, 2009) and the solutions that made THA the operation of the century (Learmonth et al., Lancet (London, England) 370:1508–1519, 2007).