Total hip arthroplasty (THA) has dramatically improved the treatment of an entire range of hip joint diseases. On the other hand, however, it has favored the development of a new disease - periprosthetic osteolysis with a consequent instability of THA. Aseptic instability is the major late complication of THA and the main reason of its malfunction. Molecular and cellular mechanisms of this complication have been thoroughly studied. The importance of prosthetic materials and design have been clearly demonstrated. However, existence of individual susceptibility to development of this complication that is determined neither by endoprothesis properties nor by demographic or morbidity characteristics of a patient has also been recognized. In the recent years, several smaller studies have tried to define the "genetic background of the individual susceptibility" towards the development of aseptic instability. All these studies followed the same logic - they searched for a link between the complication and genes coding for mediators of inflammation and/or bone remodeling, particularly those with known polymorphisms that influence expression/activity. Several associations have been found indicating, at least theoretically, a potential of developing a system of relatively reliable individual risk prediction, which in turn could result in individualized choice of prosthetic material, postoperative therapy programs and medication therapy. However, this research is at an early stage and future efforts should be focused on a) identification of genetic markers - reliable predictors and b) identification of functional links between particular genetic markers and aseptic instability. It is impossible to meet these goals without application of techniques of proteomic analysis.