Fast intrinsic optical signals (IOSs) correlated with stimulus-activated retinal responses are reviewed. Fast IOSs have a time course comparable to the stimulus-evoked electrophysiological kinetics of the retina, and thus promise a new methodology for high-resolution evaluation of the physiological health of the retina. However, practical application of fast IOSs for retinal study and diagnosis is challenging because of their low sensitivity and limited specificity. Using isolated amphibian retinas, a series of experiments to optimize and characterize fast IOSs has been conducted. Fast, high-resolution nearinfrared light imaging disclosed both positive (increasing) and negative (decreasing) optical responses in adjacent retinal areas, which satisfied spatial resolution essential to the differentiation of IOSs from opposite polarities. At the subcellular (∼μm) level, fast IOSs often exceeded 5% ΔI/I, where I is the dynamic optical change, and I is the background light intensity. Experiments with isolated frog retinas suggest that negative IOSs stem primarily from the photoreceptor layer, while positive IOSs come from inner retinal layers.