Immunoglobulin G4 (IgG4) is the least abundant subclass of IgG, playing a role in the activation of antibody-dependent immune effector responses. Raised serum IgG4 levels occur in healthy individuals and in response to various stimuli, including allergens, parasites, autoimmune reactions, and malignancy. IgG4-related disease was first identified in 2001 and is an idiopathic, chronic, fibro-inflammatory disease characterized by the infiltration of tissues and organs by T and B lymphocytes, IgG4-secreting plasma cells, and varying degrees of fibrosis, which responds to oral steroid therapy. Sites affected include salivary glands, lungs, kidneys, orbit and lacrimal glands, pancreas, biliary system, and retroperitoneum. In 2011, a team from the Ministry of Health, Labor and Welfare (MHLW) of Japan published the first comprehensive clinical diagnostic (CCD) criteria, which were updated in 2020. In 2019, the American College of Rheumatology/European League Against Rheumatism (ACR/EULAR) published a diagnostic criteria checklist for IgG4-related disease. Although glucocorticoids are effective, concerns about steroid toxicity have driven recent studies to identify effective glucocorticoid-sparing therapies, including B cell-targeted therapies. However, because the cause and pathogenesis remain enigmatic, the terminology for specific lymphoplasmacytic and fibrosing conditions (such as chronic periaortitis), which have a known immunological cause, has resulted in a broad differential diagnosis for a condition currently diagnosed by exclusion and association criteria. This article aims to review the current status and future developments in understanding the pathogenesis of IgG4-related disease, which may lead to more specific diagnosis and treatment options.