5-Fluorouracil has been the basis of chemotherapy for colorectal cancer over the past 40 years. Various methods of administration of this drug have been investigated to identify the most efficacious form of administration. Two other agents in common usage are Irinotecan and Oxaliplatin. Both of these are being studied to determine their role as primary or second line agents and their efficacy in combination with each other and 5-FU. New agents undergoing development include COX2 inhibitors and epidermal growth factor receptor inhibitor targeting drugs i.e. Cetuximab, Tyrosine kinase inhibitors and Vascular endothelial growth factor receptor inhibitors. This article reviews the above mentioned drugs and includes a recommended approach to chemotherapy in metastatic colorectal cancer.