Acute cholangitis is a potentially life-threatening systemic disease resulting from a combination of infection and obstruction of the biliary tree, secondary to different underlying etiologies. Common causes of cholangitis (eg, gallstones, benign and malignant biliary strictures) are well known. However, others (eg, immunoglobulin-G subclass-4-related sclerosing cholangitis) have been described only recently, are still under evaluation, and need to gain broader attention from clinicians. The diagnosis of acute cholangitis is based on clinical presentation and laboratory data indicating systemic infection, as well as diagnostic imaging modalities revealing signs of biliary obstruction and possibly an underlying etiology. The clinical presentation varies, and initial risk stratification is important to guide further management. Early medical therapy, including fluid resuscitation and appropriate antibiotic coverage, is of major importance in all cases, followed by a biliary drainage procedure and, if possible, definitive therapy of the underlying etiology. The type and timing of biliary drainage should be based on the severity of the clinical presentation, and the availability and feasibility of drainage techniques, such as endoscopic retrograde cholangiopancreatography (ERCP), percutaneous transhepatic cholangiography (PTC), and open surgical drainage. ERCP plays a central role in the management of biliary obstruction in patients with acute cholangitis. Endoscopic ultrasound-guided biliary drainage recently emerged as a possible alternative to PTC for second-line therapy if ERCP fails or is not possible.