Increased vascular stiffness has been identified as an important cardiovascular event that accompanies aging and cardiovascular disease. Although multiple vascular changes have been identified and suggested to cause increased vascular stiffness, our understanding of the underlying mechanisms needs to be refined in order to develop useful therapeutic strategies to prevent or reverse these changes. An example of critical questions includes: What is time course? What is its regional distribution? How does it impact microvascular function? How are vascular smooth muscle and endothelial cells involved? How do we move our understanding of the changes in the content and type of extracellular matrix proteins toward understanding architecture?