Aseptic loosening attributable to wear-related osteolysis historically has been the predominant cause of failure in THA. Advances in low-wear bearing couples show great promise to substantially reduce this long-standing problem. However, there always has been striking variability in wear rate in any given cohort of patients who are similarly implanted, with some individuals typically experiencing near order-of-magnitude elevations above group mean. Third-body wear is likely a major contributor to many of these most osteolysis-prone outliers. For the patients affected, third-body effects may obviate many of the gains otherwise achieved by contemporary bearing surface improvements. Toward heightening visibility in terms of consequences for patients, this review paper summarizes an interrelated series of investigations quantifying construct level manifestations of third-body wear. Long-term followup of a unique group of patients with elevated third-body challenge shows statistically significant and clinically important wear-rate increases. A series of finite element models, validated physically, shows the linkage of location of third-body damage with variability of volumetric wear-rate acceleration and shows the effects of various implant factors, surgeon factors, and patient factors in the presence of third-body challenge. Finally, a mechanism for third-body debris access to wear-critical locations on the bearing surface is identified analytically and corroborated in laboratory experiments and implant retrievals.