For four decades, 5-fluorouracil was the only option available for patients with metastatic colorectal cancer. It provided a response rate of 15% to 20%, with a median survival of approximately 1 year. In the past 5 years, remarkable progress has been made in colorectal cancer research with the approval of irinotecan and oxaliplatin. Most recently, targeted therapies including bevacizumab and cetuximab were added to the armamentarium. Use of two to three lines of combination therapies has raised the median survival to almost 2 years. New and promising targeted and cytotoxic therapies are currently being studied and will ideally continue to extend the median survival as well as improve the quality of life of patients with colorectal cancer.