Alterations in pancreatic cell function and morphology are characteristics of pancreatic compromise in various pathophysiological conditions. The present review focuses on potential patterns of pancreatic cell death, apoptosis, and/or oncosis, after different experimental challenges, to understand their potential significance in the pathogenesis of pancreatic injury. Apoptosis is not only present during maintenance of pancreatic homeostasis but can also be initiated by extrinsic and intrinsic factors. Pancreatic cell oncosis is another pattern of cell death, occurring in pancreatic injury. The proportion of apoptosis and oncosis may depend on the severity of pancreatic cell compromise, the properties of the challenge, animal strain, and time course. The role of various inflammatory mediators and adhesion molecules, the use of transgenic animals, and the significance of apoptosis and oncosis in acute and chronic pancreatic injury are discussed. Molecular biology of pancreatic cell death provides valuable information to simplify the understanding of mechanisms in clinical pancreatic diseases and may also introduce potential modes of pharmacological management.