Racemic ketamine, at subanesthetic doses, has shown rapid and prolonged antidepressant effects in treatment-resistant patients with major depressive disorder, bipolar disorder, and other severe psychiatric conditions. This has led to an increase in off-label use in the USA. Its (S)-enantiomer, esketamine, has been approved as a new patented intranasal treatment for treatment-resistant depression in the USA, Canada, and several European countries. However, there are concerns about esketamine’s potential adverse effects, including long-term efficacy, addiction risks, and the possibility of increased suicide risk in clinical settings when using nasal spray. Conversely, in rodent models of depression, arketamine, the (R)-enantiomer of ketamine, has demonstrated more effective and longer-lasting antidepressant action with fewer side effects than esketamine. However, research on the efficacy and safety of arketamine in patients with depression remains limited. This chapter provides an overview of arketamine’s history and its potential as a treatment for various psychiatric and neurological disorders, including depression, cognitive impairment, Parkinson’s disease, and stroke.