Many psychiatric professionals are unfamiliar with gamma-hydroxybutyrate (GHB), an increasingly popular drug of abuse. GHB withdrawal can lead to psychosis and agitation, and patients may present to psychiatric facilities for treatment. Withdrawal may progress to delirium, with the potential for severe or even fatal medical complications. Therefore, it is imperative for psychiatric professionals to understand how to treat these patients. In this article, we describe two cases of severe GHB withdrawal syndrome that were treated in our inpatient psychiatric unit. These are among the most severe cases reported. Pertinent literature is reviewed and suggestions for treatment are discussed.