The final results of two very important randomized trials of irinotecan (Campto, Rhône-Poulenc Rorer, Antony, France) as second-line treatment for patients with advanced colorectal cancer are presented. In one trial, the new topoisomerase inhibitor was compared with best supportive care; in the other, its use was compared with the strategy of high-dose 5-fluorouracil (5-FU) infusion. In both trials, patients randomized to irinotecan experienced superior survival. In the comparison against best supportive care, patients treated with irinotecan also had a significantly superior quality of life. In the comparison with infusional 5-FU, the more effective antitumor activity of irinotecan may have helped maintain quality of life. These results have implications for clinical practice: following failure on 5-FU, irinotecan must now be considered the best available option for treatment.