The serious clinical implications of contrast-induced nephropathy (CIN) have focused researchers on prevention strategies. Increased coverage of CIN in major medical journals and at major cardiovascular meetings, including the Transcatheter Cardiovascular Therapeutics (sponsored by the Cardiovascular Research Foundation), American College of Cardiology, and American Heart Association conferences, highlight this concern. Development of CIN prevention strategies is ongoing, but efforts have been hampered by an incomplete understanding of CIN pathophysiology. The most popular theories include contrast-induced renal tubular ischemia, free radical formation, and a direct tubular toxic effect. Proponents of an ischemia model direct clinical trials evaluating the efficacy of a variety of vasodilators, while those who favor a free radical or direct toxicity theory study antioxidants and free radical scavengers, or a variety of contrast agents varying in osmolality, ionicity, and viscosity. A comprehensive review of the more important and contemporary CIN prevention trials is provided to assist the cardiologist, radiologist, or nephrologist in developing his or her own data-driven approach to CIN prevention.