Microscale heterogeneity in the extracellular matrix (ECM) provides spatial information that allows tissues to develop and function properly in vivo. This heterogeneity in composition (chemistry) and structure (geometry) creates distinct microenvironments for the cells that comprise a tissue. In response, populations of cells can coordinate their behaviors across micrometer-to-millimeter length scales to function as a unified whole. We believe techniques to mimic the microscale heterogeneity of the ECM in vitro will revolutionize studies that examine how large groups of cells interact. Micropatterned ECMs used for engineering perfused microvascular networks and functional epidermis and for understanding symmetry-breaking events in epithelial morphogenesis illustrate potential applications in tissue engineering and development.