Surgery is the primary modality for cure in patients with localized colorectal cancer. However, despite potential curative surgery, the risk of recurrence is high. In colon cancer, the role of adjuvant chemotherapy with 5-fluorouracil (5-FU) and leucovorin (LV) is now established in stage III disease. The benefit of adjuvant treatment in stage II disease is likely to be small, and studies performed thus far have been generally underpowered to detect what might be a clinically significant effect on survival. Whereas bolus scheduling of 5-FU and LV is favored in North America, infusion of 5-FU/LV is preferred in Europe. Indeed, infused 5-FU/LV may be a safer partner with new drugs such as oxaliplatin and irinotecan. Oral fluoropyrimidines are attractive agents that might one day replace parenteral 5-FU. In rectal cancer, postoperative combined chemoradiation was recommended as standard practice in stages II and III disease. Despite a lack of randomized data demonstrating clinical benefit, preoperative chemoradiation has been increasingly used in patients with T3 disease in North America. However, preoperative radiation therapy is more frequently used in Europe. There are discrepancies in pathologic reporting of circumferential resection margin involvement and lymph node status between the United States and Europe. Standardized reporting with improved preoperative imaging would allow patients with truly early-stage disease to undergo more conservative management and be spared the morbidity and mortality of unnecessary adjuvant or neoadjuvant treatment.