Implant retrieval analysis offers the opportunity to investigate the causes for failure and mechanisms of wear occurring in vivo, and the biological responses to the wear debris generated during those wear processes. Although the ASTM standard F561 [“Standard for the Retrieval and Analysis of Medical Devices, and Associated Tissues and Fluids,”Annual Book of ASTM Standards, ASTM International, West Conshohocken, PA] recommends a multifaceted analysis (tissue histopathology, chemical analysis for trace metal content, wear particle isolation and characterization, and component analysis) that proceeds from least destructive methods such as visual inspection to destructive means, such as metallographic analysis, typically, only one of these aspects is the focus of published studies of failed metal-on-metal implants. This paper reiterates the advantages of a comprehensive, multifaceted retrieval approach, involving the examination of the radiographic and clinical data, the measurement of wear and characterization of damage via CMM, SEM, semi-quantitative histological analysis of tissue, and the morphological and chemical characterization of wear debris from associated tissues and fluids. The results of these analyses are then correlated with clinical, implant, and surgical factors to establish relationships and risk factors for wear and failure.