The term of biliary tract cancer (BTC) refers to all tumors that arise from the biliary tract or the biliary drainage system, including the intra- and extra-hepatic bile ducts as well as the gallbladder. BTCs are aggressive tumors with limited treatment options and poor overall survival. Currently, surgery remains to be the only potentially curative treatment, and most patients develop recurrence. For advanced tumors, only limited effective treatment modalities exist today. Gemcitabine plus cisplatin is considered as a standard option for advanced biliary cancer. A randomized phase III trial (ABC-02 trial) showed superiority of gemcitabine plus cisplatin over gemcitabine alone. In that study, they showed that after a median follow-up of 8.2 months, the median overall survival was 8.1 months in the gemcitabine-only group and 11.7 months in the gemcitabine plus cisplatin group (p<0.001). However, while this is a definite advancement, a 3-month survival extension among patients with BTC is modest at best. Moreover, this regimen has not been compared head-to-head with other gemcitabine based combinations. Gemcitabine monotherapy, 5-fluorouracil plus leucovorin, and single-agent capecitabine are all reasonable options for patients with a borderline performance status. Recent advancements have provided new insight into the genomic landscape of BTCs, and thus, it remains unclear whether combined treatment with molecular targeted agents or other cytotoxic chemotherapeutic agents may also be effective against advanced BTC.