Both hepatic parenchymal and biliary tract diseases are common in patients with human immunodeficiency virus (HIV). In this paper, the authors focus mainly on clinical aspects of acquired immunodeficiency syndrome (AIDS)-related cholangiopathy. Although the etiology is unclear, several opportunistic infections (cytomegalovirus, Cryptosporidium and others) are suspected to cause it. Endoscopic retrograde cholangiopancreatography (ERCP) is the diagnostic gold standard and it offers a therapeutic means to provide symptomatic relief in case of papillary stenosis. The most common ERCP pattern is diffuse sclerosing cholangitis in combination with papillary stenosis. Clinically, the presentation may be variable, although right upper quadrant pain and fever accompanied by an elevated serum alkaline phosphatase (ALP) level are the most common manifestations. Jaundice is unusual suggesting that complete ductal obstruction is rare. While ERCP results and the need of sphincterotomy do not influence the prognosis, antiretroviral therapy is a protective factor and, on the contrary, high ALP level is related to a less favorable outcome. Regarding the possible pathogenic mechanisms through which HIV infection could be involved in AIDS-related cholangiopathy, in vitro experiments have shown that concurrent active HIV replication and Cryptosporidium parvum infection synergistically increase cholangiocyte apoptosis and thus jointly contribute to AIDS-related cholangiopathies.