Colorectal cancer is one of the leading causes of cancer deaths in the Western world, with approximately 50% of all patients dying from metastatic disease. Until recently, therapeutic options for advanced colorectal cancer were mainly confined to chemotherapy with 5-fluorouracil in various schedules, with or without biochemical modulation with leucovorin. The development of new cytotoxic drugs with substantial activity in this tumor during the past 2 years has dramatically changed treatment strategies and therapeutic goals in metastatic colorectal cancer and has introduced neoadjuvant chemotherapy followed by secondary surgery with the intent of long-term survival. Among these new drugs, oral fluoropyrimidines (tegafur/uracil and capecitabine), irinotecan, and oxaliplatin have already established themselves as part of various treatment approaches. Other novel therapeutics including agents designed to act on molecular targets already show promising activity and will become part of combination protocols with current standard chemotherapy.