Biliary tract cancers (BTCs) are an aggressive and notoriously difficult-to-treat group of cancers, representing ~7% of all gastrointestinal malignancies. Although surgery is historically considered the only means of a cure in this disease, most patients are diagnosed in advanced stages and have abysmal survival rates based on current therapy standards. Despite many immunotherapy breakthroughs across various solid tumor types over the past decade, management of BTCs has remained largely chemotherapy dependent, with no front-line approvals of immunotherapy drugs by the USFDA at this moment. However, there is growing evidence that BTCs are an immunogenic group of cancers. Clinical research in this domain is gaining momentum, as exemplified by the recently reported TOPAZ-1 study – the first Phase III trial to show a survival benefit with immunotherapy in BTC in the front-line setting and will likely lead to approval of durvalumab. This chapter will outline the complexities of the tumor microenvironment (TME), which is essential to understanding the biology from which BTC tumor cells survive and evade the host’s immune system, but also make these cells susceptible to immunotherapies. The chapter will also discuss the key immunotherapy clinical trials that represent recent advances in BTC treatment, review the different strategies and rationales for which these therapies are given (i.e., monotherapy or combination therapy), and discuss the existing types of immunotherapies (i.e., immune checkpoint inhibitors, vaccine therapies, and cellular therapies). The conclusion will identify both obstacles in immune-oncology for BTC as well as exciting future developments in this area that can overcome some of these shortcomings.