The selective antineoplastic effect of tegafur and uracil (UFT) is attributed to its preferential enhancement of fluorouracil concentration in tumor tissues compared with that in normal tissues. The result of this effect is evident in the clinical benefit and lower toxicity associated with UFT compared with other fluorinated pyrimidines. Beginning with preclinical studies in the 1980s, significant therapeutic advantages of UFT have been reported in numerous trials conducted in Japan, including phase I dose-finding studies, phase II multicenter studies, comparative studies, and combination-chemotherapy studies. In phase II studies conducted at 211 institutions, for example, it was shown that the response rate was over 30% in patients with head/neck, bladder, or breast cancer, and the survival rate was superior to that previously reported in Japanese studies. Two comparative studies suggested that UFT was more effective than single-agent tegafur, and a number of combination-chemotherapy studies have shown that it has an advantage in terms of toxicity, response, and/or survival. UFT is also useful for postoperative adjuvant therapy, as well as therapy for advanced disease in a variety of neoplasms. UFT holds considerable promise and future trials should continue the evaluation and refinement of its role in the treatment of cancer.