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Cetuximab (Erbitux, IMC-C225, ImClone Systems Incorporated, New York, NY) is a monoclonal antibody targeted to the epidermal growth factor receptor. Expression of the epidermal growth factor receptor is associated with disease progression, poor survival, poor response to therapy, and the development of resistance to therapy in many solid tumors. Cetuximab blocks the binding of natural ligands to the epidermal growth factor receptor, thus inhibiting oncogenic processes associated with its activation. Infusion reactions, acneform skin rash, and nail disorder are the most clinically relevant adverse events observed. Because infusion reactions can be life threatening when severe, nurses must administer prophylactic treatment with an H1 antagonist prior to infusion and actively manage cetuximab-related infusion reactions when they occur. Management of infusion reactions typically includes vigilant patient monitoring, appropriate medical supervision, readily available resources for the treatment of infusion reactions, and initiation of institution- or practice-specific protocols when necessary. Acneform skin rash is the most common adverse event, but severe (grade 3 or 4) rash requiring interruption of treatment is not common. Topical and systemic antibiotic therapies may be administered to reduce symptoms. Nail disorder typically is mild to moderate and is observed infrequently; this also may be treated with systemic and topical antibiotics. Overall, the safety profile of cetuximab is favorable compared to that typically seen with chemotherapeutic agents. The acneform skin rash and nail disorder, which may affect quality of life, rarely threaten the general well-being of patients and typically are manageable.