Psilocybin is a hallucinogenic tryptamine and the main indole alkaloid present in the commonly known “magic mushrooms.” It functions as a prodrug, being extensively and rapidly dephosphorylated into psilocin after ingestion. This metabolite is ultimately responsible for the psychological and physiological effects of psilocybin, after binding to the serotonin type 2A 5-hydroxytryptamine (5-HT2A) receptor. In recreational settings, fresh/dried magic mushrooms are the consumed form of psilocybin, its use displaying a high prevalence among male adolescents and young adults, although being illegal in most worldwide countries. Adverse effects commonly reported include hallucinations, agitation, confusion, nausea, vomiting, mydriasis, tachycardia, and hypertension, the treatment being only supportive. There are also reports on more severe effects, namely persistent psychosis and myocardial infarction. In general, low toxicity and abuse potential are associated with psilocybin’s consumption. However, if consumed without a sober supervisor, in combination with other substances, and/or by individuals with self or family history of medical conditions, fatal outcome might occur. In this chapter, a comprehensive compilation, regarding psilocybin and magic mushrooms’ patterns of use, legal status, abuse potential, adverse effects and toxicity, drug-drug interactions, and methodologies applied for the toxicological examination of authentic samples, is delivered. © Springer Nature Switzerland AG 2022.