Tumors of the biliary tract (gallbladder tumors, cholangiocarcinomas and ampullary carcinomas) are low incidence tumors with poor prognosis. The five-year overall survival is 50% for stage Ⅰ, 30% stage Ⅱ, 10% stage Ⅲ and 0% stage Ⅳ. Treatment is based on surgery for potentially resectable tumors. Chemotherapy and chemo-radiotherapy is the treatment of choice when surgery is not amenable, however it has not achieved encouraging results. These patients use to have very few symptoms, which is the reason for the delay in diagnosis and the poor prognosis. They frequently develop biliary obstruction: obstructive jaundice, right upper quadrant pain and weight loss. Ampullary carcinomas are frequently related to steatorrhea due to malabsorption. The most effective chemotherapy drugs used in monotherapy are 5FU (response rate 20%) and gemcitabine (response rate of 13%-60%), so they have been selected for further development in multiple phase Ⅱ clinical trials to explore their efficacy and safety in combination with other agents. In a phase Ⅲ clinical trial, combination of gemcitabine and cisplatin has been selected as the schedule of choice. Target therapies are also being developed in this malignancy. The present work reviews the most current knowledge of the pathogenesis, diagnosis and natural history of biliary tract tumors. Further, review of surgery, current adjuvant treatment and therapies for unresectable and advanced disease is provided. The most recent understanding for target therapies and molecular biology is also summarized. Tumors of the biliary tract (gallbladder tumors, cholangiocarcinomas and ampullary carcinomas) are low incidence tumors with poor prognosis. The five-year overall survival is 50% for stage I, 30% stage II, 10% stage III and 0% stage IV. Treatment is based on surgery for potentially resectable tumors. Chemotherapy and chemo-radiotherapy is the treatment of choice when surgery is not amenable, however it has not achieved encouraging results. These patients use to have very few symptoms, which is the reason for the delay in diagnosis and the poor prognosis. They often develop biliary obstruction: obstructive jaundice, right upper quadrant pain and weight loss. Ampullary carcinomas are frequently related to steatorrhea due to malabsorption. The most effective chemotherapy drugs used in monotherapy are 5FU (response rate 20% ) and gemcitabine (response rate of 13% -60%), so they have been chosen for further development in multiple phase Ⅱ clinical trials to explore their efficacy and safety in combination with other agents. In a phase Ⅲ clinical trial, combination of gemcitabine and cisplatin has been selected as the schedule of choice. Target therapies are also being developed in this malignancy. The present work reviews the most current knowledge of the pathogenesis Further, review of surgery, current adjuvant treatment and therapies for unresectable and advanced disease is provided. The most recent understanding for target therapies and molecular biology is also summarized.