Significant advances in the treatment of colorectal cancer have been observed over the past several years. With the introduction of oxaliplatin combined with infusional 5-fluorouracil and leucovorin, survival for patients with metastatic colorectal cancer has nearly doubled. The incorporation of biologic agents that target angiogenesis (bevacizumab) and tumor growth pathways (cetuximab, panitumimab) extends survival even further, in addition to increasing response rates in patients with metastatic disease. The benefit of these newer drugs is also being realized in the adjuvant setting, where the addition of oxaliplatin to infusional 5-fluorouracil and leucovorin has led to improvements in 3-year disease-free survival. Future challenges with the use of oxaliplatin include defining strategies to optimize its use while avoiding treatment-limiting neurotoxicity and identification of markers predictive of response.