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Ketamine, an N-methyl-D-Aspartate receptor antagonist, has been used for more than 50 years. From its initial potential as an anesthetic drug, its use has increased in the fields of pain medicine, psychiatry, and palliative care. It is available in different formulations, of which oral use is promising due to its active metabolite, norketamine which reaches 2–3 times higher levels when administered orally in comparison with parenteral use. Oral use is also more feasible and easier to use in settings, where medical staff is not that present, such as home care or hospices. Oral solution of ketamine has not yet been officially licensed for use although there have been several reports which recommend its use in neuropathic pain, severe depression, airway obstruction, and anxiety. Palliative care is defined as total care for patients whose diseases do not respond to curative treatment. It encompasses good control of physical symptoms, and psychological, social and spiritual problems. Patients often experience pain, despite high doses of opioids, depression and anxiety, and dyspnea. Oral ketamine does not have the side effects of opioids therefore it represents a good alternative. It may also reduce the need for high opioid doses and be more suitable for patients who wish to avoid the necessary sedation.