5-fluorouracil/leucovorin, with or without oxaliplatin or irinotecan, is the most widely used treatment for the metastatic as well for the adjuvant setting of colorectal cancer. These agents are administered intravenously (by bolus or infusion), thereby causing significant inconvenience to patients. Capecitabine, an oral fluoropyrimidine, has been demonstrated to be at least as effective as bolus 5-fluorouracil/leucovorin in terms of time to disease progression, time to treatment failure, and overall survival, but achieves significantly higher response rates and has the advantage of oral administration. In addition, capecitabine has improved tolerability with a significantly lower incidence of stomatitis, nausea, and alopecia than 5-fluorouracil/leucovorin. Clinical trials have shown that combination therapy with capecitabine and either irinotecan or oxaliplatin is effective and well tolerated. The combination of capecitabine plus oxaliplatin, with or without bevacizumab, could represent the new standard of care for metastatic as well as surgically resected high-risk stage II and III colon cancer patients. Some pharmacoeconomic analyses have highlighted that capecitabine plus oxaliplatin results in cost savings compared with 5-fluorouracil/leucovorin plus oxaliplatin.