Acute pancreatitis is a common, often severe disease with multiple causes. Many of the aetiological factors responsible for triggering acute pancreatitis have been identified but the pathophysiological mechanism by which they do so is still poorly understood. Free calcium ions within the cytosol of the acinar cell ([Ca2+]i) act as a key intracellular second messenger in the processes of stimulus-secretion coupling and may be crucial in the pathogenesis of acute pancreatitis. [Ca2+]i signals have been shown to be disrupted early in experimental pancreatitis, and it is known that an abnormal rise in [Ca2+]i is toxic by a variety of mechanisms. It has been demonstrated that abnormal, prolonged elevations in [Ca2+]i result from caerulein hyperstimulation and ethanol treatment, and it is likely that all the known causes of acute pancreatitis can cause similar disruptions. Elevations in [Ca2+]i have also been shown to be associated with both acinar cell vacuolization and intracellular enzyme activation, both of which are key steps in the pathogenesis of acute pancreatitis. A disturbance of intracellular Ca2+ signalling and the generation of an abnormal elevation in [Ca2+]i appears to be the common factor linking all the known triggers for acute pancreatitis and initiating the further sequence of pathological events leading to clinical disease.