Abstract: Immunoglobulin G4-related disease (IgG4-RD) is an immune-mediated chronic fibroinflammatory disease first recognized in the beginning of the 21st century, affecting nearly all organs throughout the body. After over two decades of exploration, significant progress has been made in the epidemiology, etiology and pathogenesis, clinical spectrum and classification, and treatment strategies for this disease. From the initial conceptual integration that consolidated multiple previously isolated conditions into a unified category, to the in-depth analysis of the roles of immune cell subsets, and further to the implementation of high-level evidence-based clinical trials for B-cell-targeting therapies, the research history of IgG4-RD exemplifies modern medicine′s continuously deepening understanding of complex and "new" diseases. This article aims to review the core advances in the field of IgG4-RD and discuss future research directions, to provide a reference for both basic research and clinical diagnosis and treatment.