Cancer patients represent a special subset of population prone to a plethora of adverse effects secondary to cancer or cancer therapy. Among the most notable adverse effects are those that cause insult to the hepatobiliary system. This subset of adverse effects is particularly concerning as it can delay lifesaving cancer therapy. Interestingly, such lifesaving cancer therapy can be the culprit of hepatobiliary disease due to toxicity. Additionally, patients with primary hepatobiliary malignancies or metastatic cancers can develop malignant biliary obstruction, hepatic tumor rupture, or liver failure due to liver tumor burden. This is a difficult clinical scenario as patients may require prompt interventions such as hospitalization, emergent biliary drainage procedures and even intensive care. This chapter deals with hepatobiliary disease that is commonly encountered in cancer patients and may necessitate intensive management.