Approved therapies for managing opioid addiction involve intensive treatment regimens which remain both costly and ineffective. As pharmaceutical interventions have achieved variable success treating substance use disorders (SUD), alternative therapeutics must be considered. Antidrug antibodies induced by vaccination or introduced as monoclonal antibody formulations can neutralize or destroy opioids in circulation before they reach their central nervous system targets or act as enzymes to deactivate opioid receptors, preventing the physiologic and psychoactive effects of the substance. A lack of "reward" for those suffering from SUD has been shown to result in cessation of use and promote long-term abstinence. Decreased antibody production costs and the advent of novel gene therapies that stimulate in vivo production of monoclonal antibodies have renewed interest in this strategy. Furthermore, advances in understanding of SUD immunopathogenesis have revealed distinct mechanisms of neuroimmune dysregulation underlying the disorder. Beyond assisting with cessation of drug use, antibody therapies could treat or reverse pathophysiologic hallmarks that contribute to addiction and which could be the cause of chronic cognitive defects resulting from drug use. In this review, we synthesize key current literature regarding the efficacy of immunotherapies in managing opioid addiction and SUD. We will explore the neuropharmacology underlying these treatments by relating evidence from studies on the use of antibody therapeutics to counteract various drug behaviors and by drawing parallels to the similar immunopathology observed in neurodegenerative disorders. Finally, we will discuss the implications of novel immunization technologies and the application of computational methods in developing personalized addiction treatments. SIGNIFICANCE STATEMENT: Significant new evidence contributing to our understanding of substance use disorders has recently emerged leading to a paradigm shift concerning the role of immunology in the neuropathogenesis of opioid use disorder. Concurrently, immunotherapeutic technologies such as antibody therapeutics have advanced the capabilities regarding applications that take advantage of these key principles. This article reviews key antibody-based treatments being studied and highlights directions for further research that may contribute to the management of opioid use disorder.