<p>Clinics across the USA advertise ketamine as an alternative solution for mental health conditions. Ketamine has expanded into a multibillion-dollar industry, with three delivery models: (1) in-person clinics offering off-label racemic ketamine; (2) clinic visits for esketamine (Spravato); and (3) telehealth services prescribing off-label racemic ketamine. About half of the market encompasses telehealth using off-label prescribing. This article describes the legal changes behind the growth of telehealth-only providers, differences in patient monitoring requirements, and implications for patient safety. While providers can legally prescribe medications off-label, providers should consider three questions to determine whether off-label prescribing is clinically and ethically appropriate. Providers should evaluate: (1) whether sound evidence exists to prescribe; (2) whether drug benefits outweigh the risks; (3) and whether prescribing serves the patient’s best interests. As a dissociative anesthetic, ketamine raises significant concerns regarding whether the purpose and function of the drug meet legal requirements for appropriate prescribing of controlled substances.</p>