There is a high prevalence of comorbid tobacco use and alcohol use disorder (AUD), affecting more than 6 million people in the US. Globally, tobacco and alcohol use rank fourth and fifth, respectively, for disability-adjusted life-years lost. Levels of alcohol use are higher in smokers than nonsmokers, and the prevalence of smoking is higher in heavy drinkers compared with nondrinkers. This relationship is driven by many different factors, including genetics, neurobiological mechanisms, conditioning processes, and psychosocial influences. Although this unique population tends to experience more negative health consequences, more severe AUD, and poorer response to treatment than those with either AUD or tobacco use disorder alone, there are currently no available treatment protocols tailored to this comorbid condition. In this review, we provide a comprehensive review of ongoing clinical research into smoking cessation options for heavy-drinking smokers (HDS) through an evaluation of the effect of promising novel pharmacotherapies as well as combination therapies, including varenicline, naltrexone, the combination of varenicline and naltrexone, and the combination of naltrexone and nicotine replacement therapy (NRT). These treatments are considered in light of the standard of care for smoking cessation, and seek to improve upon the available guidelines for this sizeable subgroup of smokers, namely those smokers who drink heavily.