The aim of this critical review was to assess the literature regarding the treatment of death rattle at the end of life to provide an update information regarding this difficult issue. To provide suggestions for future research agenda, the approach was analytic and based on clinical considerations, rather than on raw evidence only. Both published and unpublished reports from an extensive search of electronic databases. Any randomized-controlled trial or clinical reports with a significant number of patients was considered. Eleven reports fulfilled the inclusion criteria in this systematic review. Four controlled studies, four comparative audits, and three clinical reports with a significant number of patients were selected. Despite anticholinergic or antimuscarinic medications are the drugs of choice in practice, there is a lack of supporting evidence for the use of anticholinergics to treat death rattle. Regardless of the methodological limitations of existing studies, an a priori observation was missed. Most studies were performed with the intent to treat rather than to prevent death rattle. However, from a pharmacological perspective, anticholinergic agents are unable to reduce the secretions once they are formed, but may just limit a further production. In conclusion, studies on the use of antisecretive agents provided only minor evidence of efficacy, ultimately raising questions about the routine inclusion of anticholinergic treatment in end of life pathways for the treatment of death rattle. However, this observation could be confuted by the use of these same drugs used earlier in a prophylactic perspective, in the context of a comprehensive management of the dying patients.