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Severe pancreatitis occurs in 20%-30% of all patients with acute pancreatitis. Pancreatic enzymes, cytokines and other active peptides, liberated from the inflamed pancreas, convert inflammation of the pancreas as a single-organ disease of the retroperitoneum to a multisystem disease. Determinations of pancreatic serum enzymes are still »the golden standard« for diagnosis of the acute pancreatitis. Out of clinically significant pancreatic enzymes, pancreatic-amylase and lipase are suggested for routine clinical determination due to available methods for their measurement. The methods are simple, and the results may be obtained rather quickly without any special equipment. Maximal diagnostic accuracy is achieved by »cut-off« values of 182 U/L for pancreatic-amylase and 656 U/L for lipase. Treatment of patients with acute pancreatitis is based on the initial assessment of disease severity. Early staging is based on the presence and degree of systemic failure (cardiovascular, pulmonary, and renal) and on the presence and extent of pancreatic necrosis. Individual clinical parameters and laboratory biomarkers, although sometimes helpful, are not sufficiently accurate to reliable assess the severity of an acute attack. Numeric grading systems with sensitivities of about 70% are commonly used today as indicators of organ failure and disease severity. Contrast material-enhanced computed tomography is used in addition to help evaluate local pancreatic morphology and the presence and extent of pancreatic necrosis. Out of all recently studied biochemical parameters for prognostic evaluation of acute pancreatitis patients, the measurement of C-reactive protein concentration appeared to be the parameter with the highest clinical accuracy. The best differentiation of moderate from severe acute pancreatitis forms is achieved by »cut-off« CRP values of 126 mg/L, 48 hours from the onset of symptoms. For this reason, CRP measurement may be used as the alternative to computerized tomography. In compliance with the postulations for evidence-based medicine, the procedures related to diagnosis, prognosis and management of acute pancreatitis are classified into four categories: certain, probable, possible and inappropriate.