Immunoglobulin G4-related disease (IgG4-RD) is a fibro-inflammatory disease characterized by organ enlargement and elevated serum IgG4 levels. In 2003, IgG4-RD was proposed as a distinct form of IgG4-related systemic disease based on a histopathological study involving patients with autoimmune pancreatitis. IgG4-RD occurs mainly in older men and can affect almost any organ simultaneously or metachronously. Pathophysiologically, IgG4-RD occurs when an autoantigen triggers an immune response characterized by Th2 predominance with increased production of cytokines, such as interleukin 4 (IL-4), IL-5, IL-10, IL-13, and tumor growth factor-β (TGF-β), in the affected organ. IL-10 and TGF-β produced by the increased number of regulatory T cells induce a switch from B cells to IgG4-producing plasma cells and fibrosis, respectively. The characteristic histological features consist of dense infiltration of lymphocytes and IgG4-positive plasma cells, storiform fibrosis, and obliterative phlebitis. IgG4-RD is diagnosed based on a combination of clinical, serological, radiological, and histopathological findings. Differentiating IgG4-RD from malignant tumors or similar inflammatory diseases in the affected organs is important. The 2019 America College of Rheumatology/European League against Rheumatism classification criteria for IgG4-RD have high diagnostic sensitivity and specificity. IgG4-RD generally responds well to treatment with steroids, and a swift response is reassuring and provides further diagnostic confirmation. However, relapses are common during tapering or after cessation of steroids. In Japan, low-dose steroid maintenance therapy is usually given to prevent a relapse. B-cell depletion with rituximab is effective in patients resistant to or dependent on steroids. Most patients with IgG4-RD who receive steroid therapy show good short-term clinical, morphological, and functional outcomes. However, long-term outcomes, such as relapse, fibrosis development, and associated malignancies, have not been clearly defined. Therefore, novel treatment strategies, including rituximab, need to be tested in international randomized controlled clinical trials.