Combined electrophysiological and fluorometric recordings have proven to be a powerful tool, especially in the field of neurobiology. With this combination it became possible to overcome three major limitations of pure electrophysiological measurements. First, high-resolution recordings from cellular compartments distant to the recording electrode became feasible, allowing, for example, the quantification of the occupancy of postsynaptic receptors (Mainen et al., 1999) and the density of voltage-gated Ca2+ channels (Sabatini and Svoboda, 2000) at the level of single dendritic spines. Second, the analysis of cellular responses not directly associated with electrical signals became possible. Examples include synaptically evoked Ca2+ release from intracellular stores (Takechi et al., 1998; Finch and Augustine, 1998) and Ca2+ buffering by endogenous Ca2+-binding proteins (Zhou and Neher, 1993). Third, the spatiotemporal extent of second messenger signals, for example, during subthreshold synaptic activity (Eilers et al., 1995a) and during the induction of synaptic plasticity (Eilers et al., 1997b), can be monitored by means of fluorescence imaging.