Acute pancreatitis is a protean disease, which usually takes an uneventful course to complete recovery. However, in about 25% of patients severe disease develops and may ultimately evolve to a life-threatening condition. New insights into the pathomechanism and natural course led to the identification of risk factors associated with enhanced morbidity and mortality. Prognosis or outcome is usually reflected by nonsurvival; however, not all known complications or risk factors are necessarily life-threatening and ultimately do not interfere with outcome. Among the local complications, such as necrosis and infection, only infected necrosis represents a definite outcome determinant. Since the turn of the millennium, pancreatitis-related organ failure, occurring either early or persistently, has gained considerable headway as a predominant risk factor of mortality and even seems to outweigh local complications in this respect. Other recent clinical factors include abdominal compartment syndrome, obesity, and comorbidity as relevant outcome determinants. The current review provides an overview about established risk factors determining the outcome of acute pancreatitis based on the latest and most important literature.