The treatment of self-injury, or self-destruction of one's own body tissue, has become a new focus for both researchers and clinicians. Traditionally, the field of self-injury has distinguished between the behaviors exhibited among individuals with a developmental disability (self-injurious behaviors [SIBs]) and those present within a normative population (nonsuicidal self-injury [NSSI]). Despite this distinction, many pharmacotherapies for self-injury have been administered for both populations. The current review begins by summarizing the available efficacy studies investigating common pharmacological interventions in the treatment of self-injury. These studies are organized based on the most empirically supported neurochemical pathways in the development or maintenance of NSSI: endogenous opiods and monoamines. Although significant advances have been made in the field, conclusions based on efficacy studies of the pharmacological interventions used in the treatment of self-injury have been somewhat inconsistent. Finally, the review includes a discussion about potential avenues in the pharmacological treatment of NSSI via animal models of self-injury. Animal models present a unique opportunity to test neurobiological theories of self-injury using a controlled, systematic approach. Clinical considerations are presented as they relate to the available research findings and best practices in the treatment of self-injury.