Optoregulated biointerfaces offer the possibility to manipulate the interactions between cell membrane receptors and the extracellular space. This Invited Feature Article summarizes recent efforts by our group and others during the past decade to develop light-responsive biointerfaces to stimulate cells and elicit cellular responses using photocleavable protecting groups (PPG) as our working tool. This article begins by providing a brief introduction to available PPGs, with a special focus on the widely used o-nitrobenzyl family, followed by an overview of molecular design principles for the control of bioactivity in the context of cell-material interactions and the characterization methods to use in following the photoreaction at surfaces. We present various light-guided cellular processes using PPGs, including cell adhesion, release, migration, proliferation, and differentiation, both in vitro and in vivo. Finally, this Invited Feature Article closes with our perspective on the current status and future challenges of this topic.