Hyperamylasemia and hyperlipasemia are frequently encountered in critically ill patients. Elevation in serum levels of pancreatic enzymes (hyperamylasemia and/or hyperlipasemia) can occur in any Intensive Care Unit (ICU) patient either as a result of true acute pancreatitis (AP) or as a manifestation of a nonpancreatic disease. On the one hand, AP can be misdiagnosed because neither amylase nor lipase is specific for pancreatitis. On the other hand, it is often not possible to discriminate true pancreatitis from complex and severe patients. It is essential to understand different non-pancreatic conditions where there is elevation of pancreatic enzymes and to identify true AP in critically ill patients without typical clinical features.