The nomenclature on adverse tissue reactions to wear debris in failed metal-on-metal articulations can be confusing. This review focuses on periprosthetic tissue reactions in total hip arthroplasty only and does not include hip resurfacing. We suggest that adverse reactions to biomaterials be classified as systemic or local. Systemic reactions include elevated serum ion levels, subsequent end-organ damage potential neurotoxicity, cardiotoxity, carcinogenicity, and teratogenicity. Local reactions may be thought of as (1) gross (metallosis, necrosis, cyst formation, and pseudotumor), (2) histological (macrophage-dominated, lymphocyte-dominated, or mixed), and (3) molecular (expression of inflammatory mediators and cytokines). Large-head metal-on-metal articulations, defined as head size >36 mm, were used primarily because of low rates of dislocation and potentially lower wear. Subsequently, unacceptably high revision rates and adverse tissue reactions prompted the withdrawal of some of these implants from the market. The spectrum of adverse tissue reactions in metal-on-metal articulations is similar among small and large head sizes, but the frequency of occurrence appears greater when large heads are used. Additionally, when the head-neck interface replaces a large head on a conventional taper (neck), it increases torque, micromotion, and instability.