Alcohol, illicit drugs, and nicotine can affect appetite and body weight, but few epidemiologic studies have examined relationships between body mass index (BMI) and substance use disorders. This study used logistic regression to examine effects of BMI and gender on risk for DSM-IV substance use disorders in a sample of 40 364 adults. Overweight and obesity were associated with increased risk for lifetime alcohol abuse and dependence in men but not women. Overweight and obesity were associated with decreased risk for past-year alcohol abuse in women. BMI was not associated with illicit drug use disorders. Overweight and obese men were at decreased risk for both lifetime and past-year nicotine dependence. Overweight women were at increased risk for lifetime nicotine dependence, and obese women were at decreased risk for past-year nicotine dependence. Further research is needed to identify reasons for observed gender differences in relationships between BMI and substance use disorders.