Neurotransmitters (NTs) play an important role in modulating global brain processes, such as arousal, attention, or emotion, and thus behavior. As a result, they are central to the pathogenesis and treatment of human neurological and psychiatric disorders, including Parkinson’s disease, Alzheimer’s disease, schizophrenia, depression, and addiction. In an effort to understand these pathways, sensors have been developed for NTs, including glutamate (Glu), γ-aminobutyric acid (GABA), acetylcholine (ACh), dopamine (DA), and serotonin. Thus far, most published genetically encoded NT sensors have been based on fluorescent proteins. Our lab has been working to develop NT sensors based on bioluminescence to take advantage of several qualities, including not requiring an excitation light source to enable minimally invasive imaging of a population of cells, lack of phototoxicity, and the ability for these light-emitting sensors to drive optogenetic actuators. We previously reported the development of a bioluminescent glutamate sensor to expand current capabilities into mesoscale recording of glutamate dynamics with a sensor that increases bioluminescent light emission in response to increased glutamate levels. We recently expanded on this initial glutamate sensor to accomplish reporting of ACh, GABA, serotonin, and glucose. The ultimate goal is to not only use bioluminescent NT sensors to report neuronal activity but also to achieve NT-dependent modulation of neural circuits. By pairing the bioluminescent NT sensors that we have developed with light-sensitive ion channels or pumps, we create NT-dependent luminopsins (NT-LMOs). The goal is to apply these NT-LMOs for selective synaptic modulation to either amplify or inhibit the postsynaptic response of a specific NT.