The association of alcohol consumption and acute pancreatitis (AP) has been well documented. Extensive research in the field of alcohol-induced AP has allowed scientists to understand the different aspects by which ethanol may alter pancreatic cellular function. However, despite the recognition and understanding of these proposed mechanisms, the basic question that remains unanswered is that although alcohol is consumed the world over, why is it that only some people develop AP? Epidemiologic data indicates a higher frequency of alcohol-induced AP in geographical locations where surrogate/home-brewed alcoholic beverages are freely available. These surrogate/home-brewed alcoholic beverages contain in addition to ethanol, higher alcohols (e.g. propanol and butanol) and other by-products/contaminants (e.g. acids, aldehydes and esters), the potential of which to induce pancreatic damage has been incompletely studied. Mutations in genes that metabolise alcohol as well as those that protect the acinar cells and the extra-acinar milieu from prematurely activated digestive enzymes (e.g. genetic mutations in SPINK1 or PRSS1 genes) have also been noted in these geographical locations. Based on the available epidemiologic, clinical and basic research data available at the present time, we propose a unifying hypothesis presenting for the first time the 'critical mass' concept. We hypothesise that it is the achievement of a 'critical mass' of damaged acinar cells that is required to trigger off the inflammatory cascade leading to a clinically recognised attack of AP. The consequence of a critical mass of damaged acinar cells is the generation of sufficient mediators to result in clinical AP. While the consumption of alcohol does damage acinar cells, the number of damaged acinar cells does not necessarily reach the 'critical mass' with every binge. Co-factors such a high fat or protein meals are required to sensitize the acinar cells by raising the metabolic state to a high level which compromises the viability of the cells. In addition, the existence of genetic mutations and / or the consumption of surrogate alcoholic beverages, by facilitating acinar cell damage, directly or indirectly, potentially hasten the achievement of the 'critical mass', leading to an attack of AP.