Drug development for many diseases would be aided greatly by accurate in vitro model systems that replicate key elements of in vivo physiology. The recent development of coculture systems of endothelial cells and vascular smooth muscle cells can be extended to high-throughput systems for the identification of compounds for angiogenesis, vascular repair, and hypertension. In this review, the various coculture systems are reviewed, and biologic interactions between endothelial cells and vascular smooth muscle cells are discussed. Key considerations in the design of high-throughput systems are presented, and selected examples are discussed.