Calcium serves as a universal intracellular messenger, controlling cellular processes as diverse as gene transcription, secretion, and electrical excitability. This versatility arises through the mechanisms by which Ca2+ signals are generated and transmitted to act over very different time and distance scales, ranging from waves with periods of minutes to transient domains at nanometer and millisecond scales. We focus on Ca2+ signals generated by clusters of inositol trisphosphate (IP3) receptor/channels that release Ca2+ from the endoplasmic reticulum into the cytosol. Channel opening is regulated by Ca2+ itself, creating positive and negative feedback loops that result in a hierarchy of signals ranging from openings of single channels and concerted openings of channels in a cluster to waves that sweep throughout a cell. The spatiotemporal patterns of cellular Ca2+ signals thus depend on the properties of the IP3 receptors, their spatial arrangement in the cell, and their interactions via Ca2+ diffusion and other mechanisms. We are studying these mechanisms utilizing novel optical imaging techniques to resolve the functioning of individual IP3 receptor/channels in intact cells, and to localize and track single IP3 receptor proteins with nanometer precision.