Human Valvular interstitial cells (VICs) are the most prevalent cells in the heart valve. They are present in all three layers of the valve; the fibrosa, the spongiosa, and the ventricularis. They are responsible for maintaining the structural integrity of the valve. Valvular tissue response to disease is characterized by a marked accumulation of VICs associated with inflammatory cells, neovascularization, increased matrix, and eventually fibrosis and calcification. Morphologically, heart valve interstitial cells have characteristics of both fibroblasts and smooth muscle cells. Human Vascular interstitial cells play an important role in both normal and diseased valves. These cells are useful tools to understand the regulation of cellular heterogeneity as it relates to valve structure and function in health and disease.