Currently used routine laboratory screening methods are not reliable in the prediction of contrast media-related adverse reactions. Cost-effective laboratory methods for various molecular markers of pathophysiologic activation have now become available. In vitro activation tests in high-risk patients may prove to be useful in the prediction of contrast-induced activation of various adverse reactions. If prior clinical evaluation of a patient suggests an ongoing pathologic process, profiling of the following molecular markers may prove to be useful and helpful in avoiding contrast-induced adverse reactions: Fibrinopeptide A, platelet factor 4, thromboxane B2, 5-HETE, physiologic inhibitors of proteases, B beta 15-42 related peptides, bradykinin/kininogen, and anaphylactozins. In patients suspected of reacting to contrast agents, a small dose of 1 to 5 ml can be injected as a bolus and molecular marker profiling on blood drawn after the infusion may prove to be useful screening tests. Additional clinical studies are needed to prove this. However, this screening test should be performed with extreme caution, since some of the patients are known to react to as little as 1 ml dose. The safety of newly developed nonionic contrast agents can be readily assessed by profiling various molecular markers of adverse reactions, which provide a more reliable and quantitative assessment of contrast-induced adverse reactions. Based on molecular marker profiling, various prophylactic agents can be given to high-risk patients to avoid contrast-induced adverse reactions.