Primary sclerosing cholangitis is a heterogenous immune-mediated disorder characterized by chronic inflammation and stricturing of the bile ducts. Though the driving pathophysiologic mechanisms remain elusive, there are several observed clinical phenotypes of the disease. The distribution of bile duct involvement, presence of concomitant inflammatory bowel disease, significant infiltration of IgG4-positive plasma cells, and overlapping features with other autoimmune disease has significant implications for prognosis and treatment. As there remains no pathognomonic finding for primary sclerosing cholangitis, a broad differential diagnosis and extensive evaluation of other underlying causes is critical to appropriate management.