Background: Drug abuse is a worldwide problem that is detrimental to public health. The potential for drug abuse extends to both legal and illicit drugs. Drawbacks associated with current treatments include limited effectiveness, potential side effects and, in some instances, the absence of or concerns with approved therapy options. A significant amount of clinical research has been conducted investigating immunotherapy as a treatment option against drug abuse. Vaccines against drug abuse have been the main area of research, and are the focus of this review. Methods: An extensive search using “EBSCOhost (Multiple database collection)” with all 28 databases enabled (including “Academic Search Ultimate”, “CINAHL Plus with Full Text”, and MEDLINE), interrogation of the ClinicalTrials.gov website, and searches of individual clinical trial registration numbers, was performed in February and March of 2022. This search extended to references within the obtained articles. Results: A total of 23 registered clinical trials for treating drug abuse were identified: 15 for treatment of nicotine abuse (all vaccine-based trials), 6 against cocaine abuse (4 were vaccine-based trials and 2 were metabolic-enzyme-based trials), 1 against methamphetamine abuse (a monoclonal-antibody-based trial), and 1 multivalent opioid treatment (vaccine-based trial). As indicated on the ClinicalTrials.gov website (Home—ClinicalTrials.gov), the status of all but two of these trials was “Completed”. Phase 3 clinical trials were completed only for vaccine treatments against nicotine abuse. Conclusion: Evidence in the form of efficacy data indicates that vaccines are not an option for treating nicotine or cocaine abuse. Efficacy data are yet to be obtained through completion of clinical trials for vaccines against opioid abuse. These findings align with the absence of regulatory approval for any of these treatments. This review further highlights the need for novel treatment strategies in instances where patients do not respond to current treatments, and while the search for efficacious vaccine-based treatments continues.