Oxaliplatin is the only third-generation platinum derivative compound that has found a place in the routine treatment of colorectal cancer (CRC). The appearance of oxaliplatin, as well as irinotecan, in the CRC treatment armamentarium has offered new standards for adjuvant treatment and greater hopes in metastatic disease. Moreover, the combination of oxaliplatin-based chemotherapy with new targeted drugs has improved response rates and survival of these patients. Despite these new approaches, the prognosis of CRC remains poor and a better understanding of the molecular pathways is needed to optimize the use of these new approaches. In this review, the authors examine the development of oxaliplatin as well as the main trials that have positioned oxaliplatin as a key drug in the treatment of CRC.