Cholangiocarcinoma (CCA) represents approximately 3% of gastrointestinal malignancies worldwide and constitutes around 10-15% of all primary liver cancers, being only second to hepatocellular carcinoma. Mortality from CCA has been on the rise in recent decades, and in the United States alone there has been a 36% increase in CCA from 1999 to 2014, with over 7000 CCA mortalities since 2013. Targeted therapies, which have been gaining interest due to their greater specificity toward cancer cells, have only recently started gaining FDA approval for the treatment of CCA. In this manuscript, we will go through the timeline of current FDA-approved targeted therapies as well as those that have gained FDA breakthrough therapy designation.