Until recently, few chemotherapy options were available to treat metastatic colorectalcancer. For years, the standard chemotherapy has been a Fluorouracil (5-FU) alone of 5-FU with leucovorin (LV) modulation. The newer cytotoxic drugs irinotecan (CPT-11) and oxaliplatin (L-OHP) has generated further improvement in survival. Additionally, improvement in convenience of drug administration has been achieved with the development of oral fluoropynmidines. In randomized trials, oral fluoropyrimidines were equally effective to bolus 5-FU and LV. Recently completed or ongoing clinical trials to study novel targeting agents have initiated a new generation of drug development such as angiogenesis inhibitors and epidermal growth factor inhibitors. Randomized trials will determine the impact of these newer agents on survival and quality of life.