Nicotine users are at greater risk of developing alcohol dependence. Conversely, alcohol is often consumed when young people test tobacco. The prevalence of smokers is high among alcohol dependent individuals and people who overconsume alcohol get more nicotine withdrawal symptoms when trying to quit tobacco and are less likely to succeed. Alcohol as well as smoking provides a high burden of disease, and combined use often causes multiplier damage effects. Alcohol dependent persons die more often from smoking-related illness than from alcohol. Nicotine cessation is more successful if alcohol advice is included. Cross-tolerance and other interactions between nicotine and opioids increase the likelihood of dependence. Tobacco smokers need higher opioid doses against pain. Despite evidence of association between smoking and chronic pain, understanding of causality is limited. Smoking is associated with an increased risk of opioid dependence. Nicotine is recognized as an important underlying factor. Further research in humans concerning the interactions between nicotine and opioids is urgent. Treatment of nicotine dependence in the medical management of opioid dependence seems promising, but at what point in the course - simultaneously, shortly after, or far behind - has yet to be determined.