This paper incorporates the findings from a multidisciplinary meeting on diabetic nephropathy and its renal and cardiovascular complications into a review article. The epidemic of obesity and the growing elderly population in the United States are primary drivers of a secondary epidemic of incipient type 2 diabetes mellitus and diabetic nephropathy. Current therapies aim to treat blood pressure, particularly with agents that block the renin-angiotensin system, to a target of 130/80 mm Hg. However, even lower blood pressure targets may be optimal. Control of hyperglycemia and dyslipidemia, smoking cessation, exercise, and weight loss all compliment blood pressure control and are achieved most effectively when the patient, provider, and health system are aligned with these goals. Once end-stage renal disease (ESRD) is reached, patients enter the highest cardiovascular risk-state appreciated in human medicine. Because of uniform access to care in the United States, advanced data systems, and circulatory system (intravascular) access in most patients, the ESRD population should be the future sampling frame for newer treatments tested in both prospective cohort and randomized trials. Cardiorenal risk, or the degree of excess cardiovascular risk incurred by patients with chronic kidney disease and ESRD, is a state offering considerable research opportunities for novel cardiovascular risk factors. Future studies should fully consider the possibility that improved outcomes would be achieved at a greater cost; thus, cost-effectiveness studies are essential for understanding the economic aspects of implementation. The goal of an ideal clinical trial would be ESRD prevention; however, pragmatic objectives such as a greater understanding of therapeutic toxicities should also be explored in this population.