Medial vascular calcification in an increasingly recognized problem in patients with diabetes and patients with chronic kidney disease. Calcification of the media is associated with significant morbidity and mortality. The phenotypic and the molecular fingerprints of medial calcification in patients with diabetes and patients with chronic kidney disease are strikingly similar. While disturbances in divalent ion homeostasis have been proposed to play a role in calcification of the media in patients with chronic kidney disease, patients with diabetes have an apparently intact bone and mineral metabolism. Chronic kidney disease as well as diabetes are now recognized as pro-inflammatory states. This review will explore the pathobiology of medial vascular calcification, review the evidence for diabetes and chronic kidney disease as pro-inflammatory states, and discuss the role of inflammation as a mechanistic link that explains the similarities in phenotypic and molecular characteristics of medial calcification in patients with chronic kidney disease and patients with diabetes mellitus.