Several investigations have discovered important physiologic links in the development of contrast-induced nephropathy (CIN). Studies using a canine kidney model showed that contrast media produce a direct cytotoxic effect on the renal structures. Also, there is increasing evidence that apoptosis is involved in CIN as a result of cell injury. It has been suggested that hemodynamic changes resulting from administration of contrast media may contribute to the development of CIN, although the data are not conclusive. Several vasoactive substances, such as endothelin, prostaglandins, nitric oxide, and adenosine, have been implicated in the pathogenesis of CIN, as have immune mechanisms. Several factors contribute to the development of CIN, including preexisting renal insufficiency, older age, diabetes mellitus, reduced left ventricular systolic function, advanced heart failure, acute myocardial infarction, and shock. The authors also present the risk score they developed to help clinicians identify patients with different responses to contrast exposure.