Immunoglobulin G4-related disease (IgG4-RD) is a systemic fibroinflammatory disorder capable of affecting nearly every organ system or anatomic site. First recognized as a distinct clinical entity in the early 2000s [1,2], IgG4-RD has since been identified as the underlying pathology of numerous conditions previously considered unrelated, including type 1 (lymphoplasmacytic) autoimmune pancreatitis (AIP), Mikulicz disease, and Riedel's thyroiditis [3,4]. The myriad presentations of the disease are united by shared histopathology, frequent co-occurrence within patients, and characteristic laboratory markers, most notably including elevations in serum IgG4 concentrations that are seen in a majority of patients [5].

Despite significant advances in the understanding of its pathogenesis and classification, IgG4-RD remains a diagnostic challenge due to its diverse clinical manifestations and similarity to various other immune-mediated and neoplastic conditions. The recognition of distinct phenotypic subsets, including proliferative and fibrotic forms of the disease, has provided a framework for understanding variations in treatment response and disease progression [6,7]. However, key questions regarding disease pathophysiology and optimal management strategies remain unanswered. This chapter aims to provide an overview of the clinical manifestations, diagnostic evaluation, and treatment of IgG4-RD, particularly highlighting the evidence for current and emerging therapeutic options for IgG4-RD.