Since its first use 40 years ago, 5-fluorouracil (5-FU) has become an unquestionable component of colorectal cancer treatment. It is also now well established that infusional 5-FU administration, in combination with leucovorin, is associated with better tolerance and at least equal efficacy than bolus administration. However, requiring catheter and infusion pumps, infusional 5-FU administration is costly, rather inconvenient for patients and potentially associated with morbidity, initiating subsequent oral chemotherapy development. To address intravenous 5-FU related issues, oral fluoropyrimidines have been developed such as capecitabine, preferentially converted to 5-FU into tumour cells, and UFT, able of bypassing intestinal dihydropyrimidine dehydrogenase. We discuss in this article current oral fluoropyrimidines achievements in colorectal cancer management.