Protein-based fluorescent probes of neuronal activity are at the core of emerging approaches to study the dynamics of neuronal circuits that are composed of heterologous cell types. The rationale behind our large effort to develop genetically encoded voltage indicators lies in the fact that these probes allow us and others to move beyond the electrophysiological analysis of individual or small numbers of cells without neglecting cellular diversity or compromising temporal resolution. Work in our and other laboratories during the last 15 years resulted in a new generation of voltage-sensitive fluorescent proteins (VSFPs) based on the voltage-sensing domain (VSD) of Ciona intestinalis voltage sensor-containing phosphatase (Ci-VSP). To this end, our laboratory explored different design principle families for these engineered proteins and characterized numerous mutational variants for each facility. We demonstrated that recent versions of VSFPs can report membrane voltage signals in isolated neurons, brain slices and living mice. The most advanced probes enable the optical recording of action potentials from individual neurons in single sweeps and voltage imaging of population activity, including synchronized activities in the gamma frequency band, from defined cell populations in acute brain slices. In living mice, VSFPs afford sufficient SNR for probing sensory-evoked responses and enables univocal detection of spontaneous electrical population activity in somato-sensory cortex during light anesthesia or quiet alertness. Along with the ability to target specific genetically-defined cell populations, VSFPs open a new experimental window for the study of the interaction dynamics of neuronal assemblies, facilitate the investigation of information processing mechanisms of the brain, such as the circuit operations involved in sensing our environment and generation of body movements, but will also be applicable to directly visualize cognitive functions.