Adjuvant therapy, believed by some to be of no benefit for colorectal cancer as recently as 10 years ago, now offers thousands of patients considerable hope after surgical resection. The first effective adjuvant regimen--combined fluorouracil (5-FU) and levamisole--described in 1989, was soon supplanted by a variety of 5-FU-based regimens, usually combined with leucovorin. Although most recent research in the adjuvant setting has focused on refining chemotherapy doses, schedules, and combinations, with the aim of improving efficacy and decreasing toxicity, investigators have also explored other approaches, such as portal vein infusion, monoclonal antibodies, interferon-alpha, and vaccines. Future directions being evaluated for adjuvant therapy of colon cancer include the use of oral fluorinated pyrimidines, which may replace current intravenous treatments, as well as the incorporation of new agents, such as oxaliplatin and CPT-11, into adjuvant chemotherapy programs.