Alcohol has had a long and complicated role in human society and health. Excessive use of alcohol causes enormous morbidity and mortality worldwide, but the health effects of alcohol use within recommended guidelines are diverse and complex. Established effects include increased high-density lipoprotein cholesterol and antithrombotic activity, providing plausible mechanisms for the observed association of moderate drinking with lower risk of coronary heart disease but higher risk of hemorrhagic stroke. However, moderate drinking increases sex steroid hormone levels and may interfere with folate metabolism, both of which are potential mechanisms for the observed associations of moderate drinking with several forms of cancer, particularly breast and colorectal. Genetic susceptibility to the effects of alcohol on cancer and coronary heart disease also differs across the population. Recommendations regarding moderate drinking must be individualized to reflect the potentially competing effects of alcohol on several chronic diseases.