Administration of chemotherapy agents can give rise to many safety issues. Extravasation of a vesicant agent causes tissue blistering and necrosis. This complication of chemotherapy administration causes additional pain and suffering in patients who are already suffering with a diagnosis of cancer. Nurses hold key responsibilities for educating patients about administration issues and following practice standards to minimize the risk of extravasation. Defining a path of shared responsibilities among team members is a critical step in assuring the safe administration of drugs classified as vesicants. This article describes a clinical practice change that is used at a large midwestern academic medical cancer center. This practice and policy change has resulted in a 90% reduction in the administration of vesicant agents peripherally, with no occurrence of extravasations in the first 6 months of implementation.