Nicotine constitutes the main addictive component of tobacco products. Unfortunately, this compound accounts for millions of deaths and diseases worldwide. Nicotine addiction is a complex phenomenon with multiple biological, psychological, and social factors. One of the challenges in treating nicotine addiction relates to its high rate of relapse, often triggered by exposure to nicotine or smoking cues. Nicotine vaccines, a novel immunological approach, serve to prevent or reduce nicotine addiction. They induce the production of antibodies that bind to nicotine and block its entry into the brain. Nicotine vaccines have shown promising results in preclinical studies but have failed to demonstrate sufficient efficacy and safety in human trials. Several factors may contribute to the limited success of nicotine vaccines: Different antibody responses, genetic and environmental factors, the complexity of nicotine pharmacokinetics and pharmacodynamics, and the heterogeneity of smoking behavior and motivation. This study reviews the rationale, mechanism, development, preclinical studies, and clinical trials of nicotine vaccines, as well as the challenges and future directions of this research field. We believe future research should focus on improving the design and delivery of nicotine vaccines, identifying biomarkers and predictors of antibody responses and treatment outcomes, exploring the combination of nicotine vaccines with other pharmacological and behavioral interventions, and evaluating nicotine vaccines’ long-term effects and cost-effectiveness.