In the last decades total hip arthroplasty (THA) has become a standard procedure with many benefits but also a few still unsolved complications, which can lead to surgical revision in 19-23% of cases. Thus, aseptic loosening and metal hypersensitivity remain challenges. The phenomenon of wear debris causes chronic inflammation, which produces osteolysis and aseptic loosening. Wear debris promotes osteoclast production and inhibits osteoblasts by secretion of pro-inflammatory cytokines. Micro-abrasions can be induced by abrasive, adhesive and fatigue wear and cause a liberation of metal ions, which lead to another immune response elicited mostly by macrophages. Another reaction in the neocapsule can be a type IV hypersensitivity reaction to various alloys, containing metals such as nickel, cobalt and chromium. Patch testing and the lymphocyte transformation test (LTT) are not the best diagnostic possibilities to exclude a postoperative hypersensitivity reaction, because of the different alignment of the epicutaneous cells compared to the periprosthetic deep tissue. This hypersensitivity reaction is mostly induced by cytokines, which are secreted by macrophages rather than lymphocytes. In cell cultures and in animal studies, multipotent mesenchymal stem cells (MSC) have been shown to play a role in improving initial implant integration, to limit periprosthetic osteolysis and also to reconstitute peri-implant bone stock during implant revision. Thus, MSC might be used in the future to prolong the durability of THA. A better understanding of the interactions between primary chronic inflammation, corrosion, osteolysis and hypersensitivity is mandatory to develop new therapeutic strategies, aiming at the reduction of the incidence of implant failures. In this article the underlying immunological mechanisms to aseptic loosening are presented.