Contrast-induced nephropathy (CIN) is the third most common cause of acute kidney injury in hospitalized patients. Diagnostic and interventional cardiovascular procedures generate nearly half the cases. Elderly patients and those with chronic kidney disease, diabetes, and cardiovascular disease are at greatest risk. Procedure-related risk factors include large volumes of contrast and agents with a high osmolality. Renal medullary ischemia arising from an imbalance of local vasoconstrictive and vasodilatory influences coupled with increased demand for oxygen-driven sodium transport may be the key to its pathogenesis. Contrast agents may also have a direct cytotoxic effect that operates through the generation of reactive oxygen species. Pre- and post-procedure administration of normal saline, isotonic sodium bicarbonate, N-acetylcysteine, and a variety of other pharmacologic agents have been used to prevent or mitigate CIN. While normal saline is generally accepted as protective against CIN, uncertainty still surrounds the role of sodium bicarbonate and N-acetylcysteine. Dialytic therapies before, during, and after exposure to contrast have been tested with mixed results. Logistical and economic disincentives argue against these modalities.