Ketamine, a dissociative anesthetic commonly used by US physicians, has recently been shown to be a powerful anti-depressant and is also capable of eliciting transpersonal experiences that can be transformative. Although currently approved in the US only for use as an anesthetic, physicians there can legally prescribe it off-label to treat various psychological/ psychiatric problems and it has been used for these non-anesthetic purposes in Argentina, Iran, Mexico, Russia, and the UK, as well as in the US. The literature on using ketamine psychotherapeutically is reviewed and two case studies using ketamine-enhanced psychotherapy (KEP) for treating death anxiety in terminally-ill people are reported. The potential importance of beginning formal research on using KEP during end-of-life for those suffering death anxiety is emphasized.