Panitumumab (formerly known as ABX-EGF) is the first fully human monoclonal antibody directed against the epidermal growth factor receptor in clinical use. It has proven to be very well tolerated alone and in combination with other cytotoxic chemotherapeutic agents. Panitumumab has demonstrated efficacy as monotherapy and with standard chemotherapeutic agents in a wide variety of cancer types, including non-small-cell lung cancer, renal, and colorectal cancer (CRC). To date, no human antihuman antibodies have been detected, and unlike cetuximab, infusion reactions are infrequent, and no premedications are required when administering panitumumab. The only significant toxicity has been a rash similar to that seen with other agents targeting the epidermal growth factor receptor, and such reactions have been predominantly mild to moderate. In metastatic CRC, panitumumab has been safe and efficacious when given with other commonly used agents in this disease, including irinotecan and fluorouracil. Current studies under way are looking at panitumumab in combination with FOLFOX (fluorouracil/leucovorin/oxaliplatin) plus bevacizumab as well as with novel agents that have yet to come into common clinical practice. Recent progress in development of panitumumab in the management of CRC is reviewed, and management of associated rash is discussed herein.