IntroductionThe classical pharmacopoeia used to attenuate drug dependence of illegal abuse, as well as nicotine, has shown poor therapeutic efficacy. Based on this clinical-therapeutic perspective, for more than a decade several researchers have developed new therapeutic strategies against nicotine addiction. These new experimental strategies are based on the design and synthesis of structural formulations of therapeutic vaccines against nicotine addiction. ObjectiveTo present a description of the development and therapeutic validation of active immunisation against nicotine. MethodA literature search was conducted in PubMed, using the words “Nicotine” and “Vaccine” as descriptors. A total of 427 articles were obtained of which 86 of them were used for this review. ResultsAt the pre-clinical level, active vaccination generates high levels of antibodies capable of recognising nicotine within the bloodstream with high specificity, attenuated by the behavioural alterations induced by various doses of nicotine. DiscussionAlthough the pre-clinical and clinical results have reinforced the therapeutic “proof of concept” of the active vaccination for the pharmacological control of the relapse to the addictive consumption of the nicotine in humans, guidelines are needed for the proposal and justification of synthesising new models of anti-nicotine vaccines for human use. ConclusionThis experimental pharmacological strategy of “immuno-protective” nature has been shown to be an effective treatment in significantly attenuating nicotine addictive use, search behaviours, and addictive use of nicotine, both at the pre-clinical level in the rodent model and in humans.