Periprosthetic osteolysis (PPOL) is a significant complication post-joint replacement, often instigated by implant wear debris, leading to chronic inflammation and bone resorption. Herein, this review summarizes the immune mechanisms of PPOL, specifically, the processes where macrophages are recruited by implant wear debris, the mechanisms by which macrophages trigger inflammatory cascades, and the role of chemokines that facilitate macrophage migration, including CCL2, CCL3, CCL4, CCL5, CXCL8, CX3CL1, and XCL1. This review highlights novel findings on these processes and suggests that illustrating these mechanisms offers promising avenues for future therapeutic strategies to prevent and treat PPOL, such as the potential use of anti-inflammatory drugs.