A unique and powerful application of BioLuminescent OptoGenetics is its use for the integration of cellular processes. Here, locally produced bioluminescence couples sensing of intracellular chemical fluctuations with modulation of the cell’s response. The most versatile approach to integration is the use of split luciferases, where two parts of the luciferase, separated by a sensing module, are reconstituted into a functional enzyme upon binding of the intracellular chemical to the sensing moiety. Resulting bioluminescent light emission activates photoreceptors, causing discrete cellular responses. Intracellular events that have been detected include calcium increase, protein-protein interactions, G-protein-coupled receptor activation, pH change, and protein phosphorylation. Cellular outcomes that have been integrated with these events are transcription, proximity labeling of proteins, protein cleavage, and activation of opsins. This paradigm allows investigators to selectively detect, and then suppress or amplify, specific biological events for studies aimed at understanding basic biological processes, as well as for potential therapeutic applications, stopping pathological processes from continuing or amplifying, and rescuing failing processes.