Chronic alcohol use has been linked to chronic pancreatitis for over a century, but it has not been until the last decade that the role of alcohol in chronic pancreatitis has been elucidated in animals and, only in recent years, in human populations. Although a dose-dependent association between alcohol consumption and chronic pancreatitis may exist, a staistical association has been shown only with the consumption of >or=5 alcoholic drinks per day. Smoking also confers a strong, independent and dose-dependent risk of pancreatitis that may be additive or multiplicative when combined with alcohol. Alcohol increases the risk of acute pancreatitis in several ways and, most importantly, changes the immune response to injury. Genetic factors are also important and further studies are needed to clarify the role of gene-environment interactions in pancreatitis. In humans, aggressive interventional counseling against alcohol use may reduce the frequency of recurrent attacks of disease and smoking cessation may help to slow the progression of acute to chronic pancreatitis.