Neuronal networks are among the most fascinating, yet complex, systems within biology. From neurotransmitter and neuromodulator signaling to intracellular changes in second messenger levels and enzymatic activities, the biochemical architecture of neuronal cells is in a constant state of flux. Biochemical dynamics are at the root of such complex processes such as neuronal development, learning and memory, and behavior. Noninvasively measuring and quantifying such dynamic biochemical states, however, remains a major challenge. In this review, we discuss the use of genetically encodable biosensors to address this challenge. Such biosensors are noninvasive, are readily modifiable to measure a vast array of biochemical processes, are able to provide real-time, quantitative measurements in single living cells, and link cellular biochemistry to physiological function. We provide a brief overview of genetically encodable biosensors and discuss several studies in which biosensors were used to answer specific questions in neuroscience, highlighting the vital role of genetically encodable biosensors in studying neuronal processes in a variety of contexts.