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Cell membranes are central to all life on earth. The lipid bilayer composing cell membranes enables discrimination between the cell and its external environment. Far from a passive bystander, the lipid membrane plays an active role in sequestering and accumulating genetic material, proteins, nutrients and ions essential for life. Indeed, cells allocate a significant portion of their energy budget to maintain an unequal distribution of ions across the cell membrane. The unequal distribution of ions across the cell membrane results in an electrochemical potential, or voltage. Rapid changes in this membrane voltage drive the unique physiology of excitable cells like neurons and cardiomyocytes. Despite the central importance of voltage in the brain and body, the full contributions of voltage changes to both physiology and disease remain incompletely characterized due to a lack of methods that can report on membrane potential with high fidelity, high throughput, and minimal invasiveness. Voltage imaging with fluorescent dyes offers a solution to this problem because it combines a direct readout of voltage changes, providing temporal resolution, with an imaging approach that offers spatial resolution. Attempts at voltage imaging with small molecules date back to the 1970s (Braubach et al. 2015; Loew 2015), and it is a measure of the difficulty of the task that voltage imaging has not yet become a wide-spread experimental approach. Rather, surrogates of voltage changes, notably Ca2+ ion fluxes have become the primary means of assessing neuronal and cellular activity. This is due, in part, to the fact that the experimental constraints on Ca2+ imaging are …