IgG is most abundant immunoglobulin in body (75–80%). It has four subclasses IgG1, IgG2, IgG3 and IgG4. IgG4 accounts for 3–6% of total serum IgG. Normal serum IgG4 is 86 mg/dl (range 8-140 mg/dL). This chapter covers the IgG4-Related Diseases and IgG4 Cholangiopathy or IgG4 Sclerosing Cholangitis or IgG4SC. IgG4-related diseases are systemic inflammatory diseases characterized by tumorous swelling of effected organ and high IgG4 plasma levels. IgG4 SC is IgG4 RD effecting large bile ducts. Most cases present clinically as perihilar mass mimicking cholangiocarcinomas.