In a 12-month period six people died from Creutzfeldt-Jakob disease (CJD) in a Melbourne hospice. CJD is a rare neurodegenerative disease, which commonly follows an explosive course unabated into the terminal phase. For the purposes of this article the care of six patients was audited using a retrospective chart review and a focus group was conducted with nurses involved in their care. The nurses faced considerable challenges as they endeavoured to provide comfort and support for these patients. The differences in the illness trajectory of CJD in relation to the more common experiences of illness progression in advanced cancer are discussed in the context of palliative care. This review focuses on the particular care issues of six people with CJD and their families at the end of life. The personal issues experienced by the nurses who provided palliative care are also explored. The need for the future development of guidelines for families and health professionals who care for people with CJD is highlighted.