Approximately 6 million Americans have combined chronic cardiovascular and kidney disease. This clinical intersection presents unique risks to the patient and unique challenges to the clinician. Observational studies have provided quantitative methods for estimating the risk of acute renal failure in patients undergoing percutaneous intervention and bypass surgery procedures. Fortunately, for the general cardiovascular population these risks are small. On the other hand, patients with chronic kidney disease have increased risks of accelerated atherosclerosis, nonfatal myocardial infarction, congestive heart failure, atrial and ventricular arrhythmias, and cardiac death. Chronic kidney disease presents difficult scenarios in using conventional cardioprotective therapy. However, there are increasing bodies of evidence to suggest the kidney and the heart can be targeted with lines of therapy, specifically with renin–angiotensin system antagonism, that benefit both systems with respect to reduction in the progression of disease, and the prevention of hard kidney and cardiac endpoints. This article will focus on the cardiorenal intersection and highlight innovative diagnostic and therapeutic strategies concerning this highrisk patient group.