Synapse-selective control of neural communication requires two independent components for pre- and postsynaptic partners and whose interaction can be controlled at the time selected by the experimenter. Interluminescence meets these criteria by placing a light-emitting luciferase in the presynaptic and a light-sensing opsin in the postsynaptic neuron, with engagement of this “optical synapse” dependent on the application of luciferin. Two distinct versions of Interluminescence have been developed. For activity-dependent Act-Int, luciferases targeted to synaptic vesicles are released upon firing of presynaptic neurons, while for activity-independent Persist-Int, the luciferase is tethered to the membrane of presynaptic neurons. Both strategies can activate or silence postsynaptic neurons with similar efficacy, and both have been demonstrated to work in mice. Interluminescence has strong potential as a modular platform technology that permits the use of luciferases and opsins ranging in brightness and light sensitivity for synapse-specific optical modulation of neural communication.