Colorectal cancer (CRC) is the third-leading cause of cancer death in the United States. With the advent of new chemotherapy drugs, such as oxaliplatin, for CRC, disease-free and long-term survival has improved in this patient population. As oxaliplatin use increases, more hypersensitivity reactions may be expected. The etiology of these reactions is unclear but may be a combination of immunologic responses. Pretreatment, treatment, and desensitization protocols are available to prevent and treat hypersensitivity reactions. Nurses' rapid assessment and management of infusion-related hypersensitivity reactions are vital to ensuring the safe administration of oxaliplatin.