Primary chemotherapy is an established treatment in selected patients with osteosarcoma and locally advanced breast cancer. In several other tumor entities this therapeutic approach is under clinical investigation. In contrast, colon carcinoma has been believed to be chemoresistant for a long period of time. Thus, no therapeutic approaches dealing with preoperative therapy have been initiated yet. Recent studies showing remission rates as high as 40% in advanced colon cancer and the proof of efficacy for postoperative adjuvant chemotherapy must now lead to reevaluation of the therapeutic approach to this tumor entity. Data from animal models as well as several tumor biologic hypotheses also point to a possible advantage for preoperative therapy in order to ameliorate relapse-free survival and overall survival in these patients. In this work we discuss potential advantages and disadvantages of primary, neoadjuvant strategies of treatment for colon cancer. Based on these pros and cons, clinical studies for a preoperative therapeutic approach appear to be justified and necessary in patients with locally advanced disease and in patients with metastases at the time of diagnosis.