The neurotransmitter serotonin influences a wide range of behaviors and biological processes through a series of serotonin receptors and transporters. Recent photochemical tools have made it possible to follow this complicated web of interactions with ever improving spatial and temporal resolution.

Serotonin (5-HT) is an endogenous neurotransmitter that plays a key role in cellular signaling. Its interactions with serotonin receptors (5-HTRs) and the serotonin transporter (SERT) influence processes as disparate as hunger, happiness, healing, and headaches. Over the last several decades, photochemical tools have been developed to observe, track, and modulate these serotonin–protein interactions. The tools tend to fit into one of four categories: photoswitches, photocages, photobiosensors, or photocross-linkers. This review examines the development and application of these photochemical tools for 5-HT, 5-HTRs, and SERT over the last ≈10 years, with an emphasis on the chemistry involved.