Family history is a powerful predictor of variation in risk of common diseases and conditions because it can represent the influence of both shared genes and shared environments. To investigate the relationship of parental smoking history with nicotine dependence and smoking rate, as well as with known psychological cofactors for smoking (depression, anxiety, alcoholism, disordered eating), we studied smoking adults who provided smoking history for both parents. We found that having two ever-smoking parents, in comparison to zero or one, was associated with higher nicotine dependence scores, cigarettes per day, and levels of anxiety in participant, with a trend for depression. Participants whose mothers smoked during pregnancy had significantly higher scores on nicotine dependence, smoking rate, and disordered eating than participants with either ever-smoking mothers who did not smoke during pregnancy or never-smoking mothers. These findings suggest that family history of smoking may be a key determinant of interindividual variation in smoking behavior, nicotine dependence, and psychological cofactors among smokers.