Accidental administration of the intravenous chemotherapy agent vincristine into the sac around the spinal cord is almost invariably fatal. This error has been recognized since vincristine was first used in the 1960s and is now classified as a never event, but it has not been eliminated despite vigorous efforts. This article reviews the history of safety initiatives around vincristine and identifies five domains of failure, ranging from failure to adequately investigate cases to failure to translate safety solutions internationally. A fatal vincristine error that occurred in the United Kingdom was the subject of a detailed investigation commissioned by the National Health Service. One of this article's authors, Sir Liam Donaldson, was interviewed by AHRQ WebM&M in 2007.