The native cell microenvironment is extraordinarily dynamic, with reciprocal regulation pathways between cells and the extracellular matrix guiding many physiological processes, such as cell migration, stem cell differentiation, and tissue formation. Providing the correct sequence of biochemical cues to cells, both in vivo and in vitro, is critical for triggering specific biological outcomes. There has been a diversity of methods developed for exposing cells in culture to spatiotemporally varying cues, many of which have centered on dynamic control over cell-material interactions in an attempt to recapitulate the role of the extracellular matrix in cell signaling. This review highlights several mechanisms that have been employed to control bioactive ligand presentation in biomaterials, and looks ahead toward the potential for genetically encoded approaches to dynamically regulate material bioactivity using light.