Chronic cholestasis is the hallmark clinical feature of primary biliary cholangitis. In addition to progressive liver damage, chronic cholestasis can lead to serious complications, many of which occur outside the liver. Bile acids are ligands for nuclear hormone receptors, and alterations in their concentration disrupt normal functioning of numerous different cell types. This article discusses the clinical presentation, pathophysiology, and management of pruritus (itching), fatigue, osteoporosis, hyperlipidemia, fat-soluble vitamin deficiencies, malignancies, cardiac dysfunction, bacterial cholangitis, cholemic (bile cast) nephropathy, and Sicca syndrome.