Psychedelic drugs, known for their perception-altering properties, are gaining popularity in the treatment of mental health and pain disorders. As exploratory studies demonstrate clinical efficacy with few adverse events, it is expected that more patients will ingest psychedelic drugs. For therapeutic reasons, as with any drug, anaesthesiologists must be aware of its physiological effects and contraindications to ensure the safe provision of anaesthesia. Psilocybin is a 5HT1A and 5HT2A serotonin receptor agonist thought to act on excitatory and inhibitory neurons in the brain. Acute ingestion causes sympathetic nervous system activation, which can precipitate haemodynamic instability. Activation of the 5HT serotonin receptors can also place the patient at risk of serotonin syndrome. Chronic use increases plasma concentrations of cortisol, which has implications on prophylactic stress-dosing of glucocorticoids preoperatively. Lysergic acid diethylamide (LSD), a synthetic psychoactive substance, is also a 5HT2A agonist. LSD has been shown to potentiate opioid analgesics, and monoamine oxidase (MAO) inhibition. Historical reports suggest that LSD has anticholinesterase activity and can prolong neuromuscular block with depolarising muscle relaxants. Mescaline is a poorly understood psychedelic with similar autonomic effects. Historical studies have shown decreased neuromuscular transmission and an association with malignant hyperthermia. When managing patients who have consumed psychedelics drugs, it is important to consider delaying surgery whenever possible, to allow acute intoxication to wane. A high degree of suspicion and an understanding of management principles is vital to the safe conduct of anaesthesia. Future research should explore therapeutic doses of psychedelic drugs to understand physiologic effects at various concentrations.