Cholangiocarcinoma is an epithelial malignancy originating in the biliary tracts and frequently recurs even with surgical resection. Unresectable disease has a 5-year overall survival of less than 10%. Given this poor prognosis, additional therapies are urgently needed. Chemotherapy has been the mainstay of treatment for many years. However, with the incorporation of immunotherapy into the treatment of other malignancies, there has been a great deal of interest in immunotherapy for biliary cancers. Recently, durvalumab was approved in combination with gemcitabine and cisplatin for the treatment of unresectable cholangiocarcinoma in the first-line setting. However, predicting which patients may respond to immunotherapy remains a challenge due to the lack of a reliable biomarker.