The article discusses the rapidly evolving landscape of ketamine in the United States, particularly focusing on its therapeutic and recreational use. Ketamine, initially approved as an anesthetic in 1970, has gained attention for its rapid and powerful antidepressant effects at subanesthetic doses. However, the off-label use of ketamine in psychiatry has grown without regulatory oversight, leading to concerns about drug diversion, overuse, and potential adverse effects. The FDA's approval of esketamine, a more regulated form of ketamine, in 2019 has not significantly reduced off-label ketamine use. The lack of regulatory oversight during the COVID-19 pandemic allowed for increased home administration of ketamine, leading to regulatory actions by federal agencies. The article highlights the potential consequences of off-label ketamine use, including unregulated clinics, overexposure to high doses, and diversion. It also notes the increasing recreational use of ketamine, driven by media attention and advertising, which has led to a rise in law enforcement seizures and poisonings. The cheap and easy availability of ketamine, often in powder form, poses significant risks, including the possibility of adulteration with substances like fentanyl. The authors emphasize the need for further research and surveillance to monitor the prevalence of medical and nonmedical use, off-label prescribing, and related adverse effects. They call for a clinical registry to better understand the issues and for increased focus on ketamine diversion and trafficking, both in psychiatric and veterinary clinics. The article concludes by urging widespread surveillance efforts to fully understand the current ketamine landscape and to detect changes quickly.The article discusses the rapidly evolving landscape of ketamine in the United States, particularly focusing on its therapeutic and recreational use. Ketamine, initially approved as an anesthetic in 1970, has gained attention for its rapid and powerful antidepressant effects at subanesthetic doses. However, the off-label use of ketamine in psychiatry has grown without regulatory oversight, leading to concerns about drug diversion, overuse, and potential adverse effects. The FDA's approval of esketamine, a more regulated form of ketamine, in 2019 has not significantly reduced off-label ketamine use. The lack of regulatory oversight during the COVID-19 pandemic allowed for increased home administration of ketamine, leading to regulatory actions by federal agencies. The article highlights the potential consequences of off-label ketamine use, including unregulated clinics, overexposure to high doses, and diversion. It also notes the increasing recreational use of ketamine, driven by media attention and advertising, which has led to a rise in law enforcement seizures and poisonings. The cheap and easy availability of ketamine, often in powder form, poses significant risks, including the possibility of adulteration with substances like fentanyl. The authors emphasize the need for further research and surveillance to monitor the prevalence of medical and nonmedical use, off-label prescribing, and related adverse effects. They call for a clinical registry to better understand the issues and for increased focus on ketamine diversion and trafficking, both in psychiatric and veterinary clinics. The article concludes by urging widespread surveillance efforts to fully understand the current ketamine landscape and to detect changes quickly.