Fluoropyrimidines remain the cornerstone of chemotherapy regimens in the treatment of metastatic colorectal cancer (mCRC), even with the availability of newer cytotoxic and targeted biologic agents (eg, irinotecan, oxaliplatin, bevacizumab, cetuximab, and panitumumab). Though 5-fluorouracil (5-FU) can be administered via bolus or infusional schedules, the intermittent infusional schedule has been a mainstay of fluoropyrimidine-based regimens. This strategy, however, requires the insertion of central venous catheters and infusion pumps, which represent major inconveniences for patients and are associated with an increased risk for complications. Capecitabine is an orally administered fluoropyrimidine carbamate that is absorbed intact from the gastrointestinal tract and becomes metabolically activated to 5-FU within the tumor. Orally administered chemotherapy gives patients greater flexibility and independence and, as a result, may improve compliance and lower overall healthcare costs. Several randomized phase III studies have demonstrated the efficacy and safety of capecitabine in mCRC, whether used as monotherapy or in combination with oxaliplatin. However, dosing has been the subject of considerable debate, and there is evidence that dosing differs among clinical practices in Europe, Asia, and North America. The optimal dose and dosing schedule of capecitabine might require individualization based on specific patient factors, such as presence of comorbid illnesses, renal function, use of other prescription and nonprescription drugs, herbal and/ or nutritional supplements, and the development of adverse events. Guidelines for capecitabine dose modification/ interruption have been developed, and they should be used when trying to optimize oral fluoropyrimidine therapy for patients with mCRC.