Introduction: Smoking remains a worldwide epidemic, and despite an increase in public acceptance of the harms of tobacco use, it remains the leading cause of preventable death. It is estimated that up to 70% of all smokers express a desire to quit, but only 3-5% of them are successful.Areas covered: The goal of this review was to evaluate the current status of smoking cessation treatments and the feasibility of implementing personalized-medicine approaches to these pharmacotherapies. We evaluated the genetics associated with higher levels of nicotine addiction and follow with an analysis of the genetic variants that affect the nicotine metabolic ratio (NMR) and the FDA approved treatments for smoking cessation. We also highlighted the gaps in the process of translating current laboratory understanding into clinical practice, and the benefits of personalized treatment approaches for a successful smoking cessation strategy.Expert opinion: Evidence supports the use of tailored therapies to ensure that the most efficient treatments are utilized in an individual's smoking cessation efforts. An understanding of the genetic effects on the efficacy of individualized smoking cessation pharmacotherapies is key to smoking cessation, ideally utilizing a polygenetic risk score that considers all genetic variation.