During the last decade, numerous new agents were introduced into the therapy of metastatic colorectal cancer. Treatment duration and maintenance therapy, however, still remain a controversial issue. More and more results from clinical trials become available that assess the role of maintenance chemotherapy in combination with the angiogenesis inhibitor bevacizumab and epidermal growth factor inhibitors. Taken together, these data suggest that some form of maintenance therapy leads to a better patient outcome and is thus appropriate. Our challenge remains the need to identify and predict the required therapeutic intensity whether by biomarkers or clinical parameters. As also side effects may increase due to drug combinations, quality of life issues need to be carefully considered for each individual patient.