Surgery currently remains the only potentially curative treatment for biliary tract cancer, and most patients develop recurrence. Thus, effective adjuvant therapy is required to increase the curability of surgery and to prolong the survival in these patients. However, to date, no standard postoperative adjuvant therapy regimen has been established for patients with biliary tract cancer. Based on favorable results reported from phase II trials, gemcitabine and S-1 are currently available as promising agents for the treatment of unresectable biliary tract cancer in Japan. Both agents are also expected to be effective in the postoperative adjuvant therapy setting for biliary tract cancer, and well-designed randomized controlled trials (phase III trials) to determine the efficacy of these agents in the postoperative adjuvant setting should be pursued vigorously. In phase III trials, appropriate stratification of patients is important, and the primary disease (gallbladder cancer versus nongallbladder cancers), curability (R0 or R1), and presence/absence of lymph node metastasis should be taken into account.