Use of hallucinogenic substances as a public health concern has increased over the past decade. Among adolescents, there are increasing emergency department presentations for intoxication with these drugs, contrary to decreasing reported use of classical hallucinogens such as LSD. Academic and governmental groups have monitored use of hallucinogens, highlighting a notable change in perceptions about use among adolescents thought to contribute to these trends. Special populations and religious groups, though, have been granted governmental permission to use hallucinogens for their cultural practices. Novel designer hallucinogens have gained popularity and may have serious medical and psychological side effects from use.