Colorectal cancer is a curable disease in stage II and stage III with higher cure rates if adjuvant chemotherapy is administered and that in most cases is treated with palliative intention in stage IV. Addition of bevacizumab, a vascular endothelial growth factor (VEGF) antibody, prolongs progression-free survival in stage IV when added to chemotherapy. Results of the NSABP study C-08 show that bevacizumab does not improve outcome when added to adjuvant chemotherapy in stage II and stage III colon cancer. Oxaliplatin led to a prolongation of progression-free survival and to improved response rates when added to 5-FU in stage IV colorectal cancer. In contrast, addition of oxaliplatin to 5-FU-based radiotherapy in neoadjuvant treated locally advanced rectal cancer did not improve the response rate. Survival results with adjuvant oxaliplatin in rectal cancer need to be awaited. The addition of oxaliplatin to 5-FU-based adjuvant chemotherapy in stage II (high risk) and stage III colon cancer became a standard of care after results of two randomized studies had been published. Current results suggest that the benefit of adding oxaliplatin in patients >70 years is vanishing and 5-FU/folonic acid alone should be considered the standard of care in the adjuvant treatment of elderly patients. Cetuximab and panitumumab are two epidermal growth factor receptor (EGFR) directed monoclonal antibodies with proven activity in stage IV colorectal cancer. K-Ras mutations indicate resistance to anti-EGFR-directed antibodies. New molecular markers like the expression of the EGFR ligands epiregulin and amphiregulin, the expression of insulin-like growth factor-1 (IGF-1) and mutations of b-RAF and n-RAS may complement the panel of markers for the selection of patients who benefit from anti-EGFR treatment.