Oxaliplatin (Eloxatin; Sanofi-Synthelabo Inc.; New York, NY) is a third-generation platinum agent indicated for the treatment of colorectal cancer. Severe hypersensitivity reactions to oxaliplatin rarely occur; however, they do represent a threat to the small number of patients that are occasionally affected. We developed a desensitization protocol and successfully applied it to a patient with severe, grade 3, hypersensitivity to oxaliplatin. For patients who have mild sensitivity to oxaliplatin, slowing the run rate down and giving an antihistamine and/or a steroid usually suffice. Desensitization will help to provide the small number of patients who experience severe hypersensitivity reactions with the ability to further receive an effective therapy for their colorectal cancer. The desensitization protocol is described in detail.