Immunoglobulin G4-related disease (IgG4-RD) is a systemic immune-mediated fibroinflammatory disease that is believed but not confirmed to have an autoimmune origin. Since its discovery nearly two decades ago, our understanding of its pathophysiology and clinical manifestations has grown substantially. Early diagnosis and treatment of this elusive disease can prevent substantial organ damage from end-stage fibrosis. This underscores the importance of prompt recognition, full characterization, and astute management. The American College of Rheumatology/European League Against Rheumatism Classification Criteria provide a framework for approaching the diagnosis of IgG4-RD even though they were not intended for diagnostic purposes. The approach to diagnosis involves recognizing the typical disease manifestations and incorporating clinical, radiological, serological, and histopathological information. The exclusion of disease mimickers, particularly malignancy and other inflammatory conditions, is essential. Both glucocorticoids and B cell depletion are effective at inducing remission in IgG4-RD in most patients. The optimal approach to the use of these agents is now being defined in clinical trials.