To date, CRP remains the single standard biochemical marker for predicting the severity of AP. Because the combination of clinico-physiological scores and CRP provides good information at 48 hours, research has focused on the predictive ability of various markers when applied in the initial 24 hours after admission to the hospital. After detailed review of the literature, the authors conclude that there is no single tool that serves as the optimal predictor of severity. There are, however, data supporting the use of certain tests to improve upon the clinician's early predictive ability on the subsequent course of AP. These include an APACHE II score greater than seven, IL-6 at the time of admission, and urine TAP, urine trypsinogen-2,and serum PMN-elastase at 24 hours (Box 1). These markers will only be able to help the clinician's predictive ability if they can be performed locally and if the results can be available in a timely manner. Future research should focus on markers such as procalcitonin, IL-8, IL-I ra, sTNFR,CAPAP, PLA-2, novel markers, and the combined use of more than one marker. The conventional research approach in predicting severity used in the last15 years has limitations and appears to have reached its maximal potential. Novel conceptions and approaches, such as identification of genetic polymorphisms that predispose to severe course and complications of AP, are needed for a quantum step forward.