Substance use is common among individuals admitted to the critical care setting and may complicate treatment of underlying disorders. It is imperative for the critical care team to have a high index of suspicion for substance intoxication and withdrawal. This article reviews the epidemiology of substance use in this population and the treatment of common withdrawal syndromes. General principles regarding the management of substance withdrawal syndromes include general resuscitative measures, use of a symptom-triggered approach, and substitution of a long-acting replacement for the abused drug in gradual tapering dose. The authors stress the importance of long-term planning as part of the overall treatment protocol beyond the acute presentation.