Drug development has undergone rapid shifts in methodology and the use of rationally derived agents which either target specific tissues or molecules such as receptors or enzymatic sites. Capecitabine is a rationally derived prodrug of 5-fluorouracil which is based upon the known high concentration of the enzyme thymidine phosphorylase in many human tumors. The first prodrug designed to exploit this biochemical finding was 5-DFUR which allowed cytotoxic 5-fluorouracil to be preferentially concentrated in tumors. Unfortunately, in man this agent was associated with significant gastrointestinal toxicity. Further manipulation of this molecular resulted in capecitabine which is a relatively inert prodrug, undergoes three enzymatic steps, and offers the potential of less gastrointestinal toxicity. Phase I trials have examined several schedules with the divided oral daily x 14 schedule every 3 weeks as the preferred phase II and phase III dosing method. This agent demonstrates significant antitumor effect in diseases known to be responsive to fluoropyrimidines. Further study is needed to determine whether capecitabine has a broader spectrum of action thus affecting other tumor types than 5-fluorouracil. Major dose limiting toxicities have been hand foot syndrome, nausea/vomiting, and diarrhea.