Oxaliplatin, a second-generation platinum analog, has evolved as one of the most important therapeutic agents in the treatment of both metastatic colorectal cancer and stage II/III colon cancer. Moreover, oxaliplatin is currently being investigated in the perioperative treatment of locally advanced rectal cancer. Oxaliplatin can be safely combined with fluoropyrimidines, irinotecan, bevacizumab and EGF receptor antibodies, resulting in increased response rates and delayed progression. In combination with EGF receptor antibodies, fluoropyrimidine schedules need to be cautiously considered. Treatment strategies to limit oxaliplatin-induced neurotoxicity by discontinuous administration schedules (e.g., induction followed by maintenance, followed by reinduction or intermittent treatment) are available.