Gall bladder cancer (GBC), and intrahepatic and extrahepatic (perihilar or distal bile duct's) cholangiocarcinomas (CCA) are usually diagnosed in locally advanced or node-positive stage, with a short survival rate. Thus, it appears essential to explore novel strategies for improving disease downstage and radical surgery. Chemoradiotherapy followed by liver transplantation seems to be one of the most promising approaches for intrahepatic or perihilar disease while chemotherapy with novel radiotherapy techniques (such stereotactic body radiation) emerged as an attractive preoperative treatment in distal diseases. In this paper, we will review currently available knowledge about neoadjuvant treatment of biliary tract cancers (BTC) paying attention to challenges that make this type of management in clinical practice difficult.