Although 5-FU administered as a single agent in different intravenous bolus schedules has been shown to have minimal activity in non-small cell lung cancer (NSCLC), several lines of experimental evidence suggest that 5-FU in combination regimens may be synergistic with the 'anchor' drug of the combination. Moreover, the recent availability of oral formulations of 5-FU together with the ability to modulate the anabolic and catabolic metabolism of 5-FU with leucovorin and dihydropyrimidine dehydrogenase (DPD) inhibitors, respectively, may provide a substantial improvement in the ease of administration and the efficacy of fluoropyrimidine therapy. Several oral fluoropyrimidines are under investigation. Orzel [UFT (uracil:tegafur) plus oral leucovorin] is the first oral DPD-inhibitory fluoropyrimidine. Orzel administered daily achieves similar concentrations of 5-FU obtained with continuous-infusion 5-FU. This paper reviews the clinical experience with UFT and Orzel in the treatment of NSCLC.