Cetuximab is a human/mouse chimeric monoclonal antibody that binds to the EGF receptor, competitively inhibiting ligand binding, and inducing receptor dimerization and downregulation. Cetuximab has been active in multiple tumors, including colorectal cancer (CRC), head and neck, pancreatic and lung cancers. Cetuximab has been approved by the FDA, in combination with irinotecan, for the treatment of metastatic CRC in patients refractory to irinotecan, and for use as a single agent in the treatment of recurrent metastatic CRC in patients intolerant of irinotecan-based chemotherapy. Most common toxicities are rash, diarrhea, fever, headache, nausea, hypomagnesemia and hypersensitivity reactions. Data from several clinical trials with cetuximab show a positive correlation between rash and response and/or survival. Rash occurred on 90% of patients treated with cetuximab monotherapy and grade 3 or 4 skin reactions occurred on as many as 16% of patients in the trials using cetuximab. A rash usually presents as pustular or maculopapular follicular eruption, often referred to as acneiform. Cetuximab will engage in productive dimerization complexes in human skin causing significant disruption of the normal development and maintenance of the hair follicle, which leads to follicular response and inflammatory response. At this time there are no standard or evidence-based treatment plans for the rash. Most of the evidence is based on institutional or personal experiences. The most commonly used agents are topical antibiotics, oral antibiotics, topical steroids, systemic immunomodulatory agents, topical immunomodulatory agents and anti-inflammatory preparations. As cetuximab is becoming widely used in general oncology practice, it is important to understand the toxicity of rash to develop practice guidelines for their management. This review addresses recommendations for toxicity management of rash caused by cetuximab in treatment of metatstatic CRC.