Calcium functions as a versatile messenger in mediating responses to hormones, biotic/abiotic stress signals and a variety of developmental cues in plants. The Ca2+-signaling circuit consists of three major "nodes" - generation of a Ca2+-signature in response to a signal, recognition of the signature by Ca2+ sensors and transduction of the signature message to targets that participate in producing signal-specific responses. Molecular genetic and protein-protein interaction approaches together with bioinformatic analysis of the Arabidopsis genome have resulted in identification of a large number of proteins at each "node" - similar to80 at Ca2+ signature, similar to400 sensors and similar to200 targets - that form a myriad of Ca2+ signaling networks in a "mix and match" fashion. In parallel, biochemical, cell biological, genetic and transgenic approaches have unraveled functions and regulatory mechanisms of a few of these components. The emerging paradigm from these studies is that plants have many unique Ca2+ signaling proteins. The presence of a large number of proteins, including several families, at each "node" and potential interaction of several targets by a sensor or vice versa are likely to generate highly complex networks that regulate Ca2+-mediated processes. Therefore, there is a great demand for high-throughput technologies for identification of signaling networks in the "Ca2+-signaling-grid" and their roles in cellular processes. Here we discuss the current status of Ca2+ signaling components, their known functions and potential of emerging high-throughput genomic and proteomic technologies in unraveling complex Ca2+ circuitry. (C) 2004 Elsevier Ltd. All rights reserved.