Dissociative substances (phencyclidine, ketamine, dextromethorphan, nitrous oxide) exert a high characterized by feelings of detachment from reality and perceptual disturbances. This class of drugs primarily targets the N-methyl-D-aspartate (NMDA) receptor and can result in complications such as psychosis and a host of other medical and psychiatric comorbidities. While the prevalence of dissociative drug addiction is low compared to other substances, the accessibility of these drugs makes them popular among youth and party-goers. This chapter explores the risk factors, pathophysiology, diagnostic criteria, and clinical manifestations associated with dissociative substance use.