Hepatopancreatoduodenectomy is one of the most challenging surgical procedures. Its role is still controversial due to the technical complexity and high risk of complications. Many advancements have been made in the treatment of hilar cholangiocarcinoma, but surgical resection with negative margins and regional lymphadenectomy still remains the only potentially curative treatment. Some advanced cases, which were considered unresectable in a not so far past, can benefit from extensive resections such as hepatopancreatoduodenectomy. Centres with high experience in hepatobiliopancreatic surgery and a careful selection of patients are essential to perform this surgical procedure.