Metallosis represents a rare and severe complication of knee replacement surgery. It is caused by the infiltration and accumulation of metallic debris into the peri-prosthetic structures, deriving from friction between metallic prosthetic components. In knee arthroplasty, this event generally occurs as a result of polyethylene wear of the tibial or metal-back patellar component. The real incidence of metallosis is still unknown, although it seems to be more frequent in hip than in knee arthroplasty. The metallic debris induces a massive release of cytokines from inflammatory cells, making a revision necessary whenever osteolysis and loosening of the prosthesis occur. We report four patients who underwent revision of their knee arthroplasty because of severe metallosis. In one of these patients, polyethylene wear had determined friction between the metal-back patellar component and the anterior portion of the femoral component. In the remaining three cases, metallosis was caused by friction between the femoral and tibial prosthetic metal surfaces, resulting from full-thickness wear of the tibial polyethylene. T lymphocytes were activated by metal particles present in periprosthetic membranes. In all patients, one-stage revision was necessary, with rapid pain disappearance and a complete functional recovery of the knee joint.