Depression is prevalent and undertreated in patients receiving hospice care. Standard antidepressants do not work rapidly or often enough to benefit most of these patients. Here, two cases are reported in which a single oral dose of ketamine provided rapid and moderately sustained symptom relief for both depression and anxiety. In addition, no adverse effects were noted. Further investigation with randomized, controlled clinical trials is necessary to firmly establish the effectiveness of oral ketamine for the treatment of depression and anxiety in patients receiving hospice care. Ketamine may be a promising safe, effective, and cost-effective rapid treatment for depression and anxiety in this population.