Colorectal cancer is one of the leading causes of cancer-related mortality. After a series of clinical trials, the adjuvant 5-FU based chemotherapy has established a definitive role in the management of stage III colon cancer. The precise role for chemotherapy in stage II disease remains under investigation and less toxic treatment modalities like active specific immunotherapy have emerged as potentially attractive alternatives. It is most likely that the adjuvant treatment of colon cancer will move towards more tumor-specific immunotherapies using antibody- or vaccination-based strategies. Phase II/III clinical trials investigating these different modalities in colorectal cancer are reviewed.