This chapter examines the expanding role of oral ketamine and S-ketamine across various clinical contexts, including management of pain, severe neuropsychiatric disorders, and palliative care patients. The oral therapeutic potential of the ketamine builds on their therapeutic value and emerging indications beyond traditional intravenous applications. Oral formulations present a promising alternative, addressing limitations of intravenous administration. However, challenges such as dose optimization, best possible use schedules, and safety issues in individual patients have not been completely clarified.