The extracellular matrix (ECM) is a highly complex composite material, with hierarchical organization, many different organic and inorganic features, and dynamic self-assembly and disassembly processes that regulate tissue homeostasis and morphogenesis. The ECM differs significantly across tissue types, where the mechanical, topographical, biochemical and transport properties of the materials are dictated in a contextual fashion to guide specific cellular and tissue level functions. The presentation of these cues to cells is not a static process, but rather a dynamic interplay between individual cells, their neighbors and the ECM architecture. This spatiotemporal control of signaling patterns in the cellular microenvironment regulates diverse functions, including quiescence, migration, proliferation, differentiation and apoptosis. Understanding how the properties of the ECM directs tissue form and function is important for fundamental biology research but also for establishing design criteria for next generation biomaterials that aim to recapitulate the structure and function of native extracellular matrices.