Patients with diabetes and kidney disease are at high risk of cardiovascular diseases, including coronary heart disease, stroke, heart failure, peripheral vascular disease, and sudden cardiac death. In fact, recent data suggest that kidney disease explains much of the excess cardiovascular risk associated with both type 1 and type 2 diabetes. Potential mechanisms relating kidney disease to cardiovascular disease range from augmentation of common risk factors, such as hypertension, to novel kidney-specific risk factors. Recent discoveries and advances in technology have highlighted small molecule “uremic toxins” that are retained in kidney disease and impairment in the regulation of mineral metabolism as promising mediators of cardiovascular risk in patients with kidney disease. These mediators highlight the multifaceted role of the kidney in maintaining homeostasis and health and offer new opportunities to reduce cardiovascular risk in diabetic kidney disease.