Cigarette smoking is a major risk factor for pancreatic cancer and probably pancreatitis. It has been reported that patients with chronic pancreatitis are 16 times more likely to develop pancreatic cancer than normal individuals. Nicotine, a major component of tobacco and an addicted drug of abuse in humans, appears to play a role in the aetiology of both pancreatic cancer and pancreatitis. This review discusses major published reports pertaining to the influence of nicotine on these diseases in humans and the probable effects of nicotine on the pathophysiology of the pancreas in animal models. A hypothetical pancreatic acinar cell model showing multiple signal transduction pathways is presented relating to possible mechanisms of action of nicotine on the pathophysiology of the pancreas.