Ca 2+ is able to bind to hundreds of cellular proteins over a 10 6 -fold range of affinities (nM to mM) (Figure 2 (a)), depending on the nature of the Ca 2+ -modulated events. Ca 2+ binding has been shown to be essential for stabilizing proteins as well as maintaining proper cellular free Ca 2+ concentrations as seen in buffer proteins such as calbindin D 9k and parvalbumin ( Figure 2 ). Generally the Ca 2+ modulated activity is achieved through Ca 2+ -dependent conformational changes in Ca 2+ -binding proteins. For example, one of the ubiquitous intracellular trigger (modulating) proteins, calmodulin (CaM), has been shown to interact with over 300 proteins [6] ( Figure 2 ). Interestingly, this protein has been recently shown to regulate a large class of membrane proteins that are essential for cell signaling and cell-cell communication such as gap junctions [6] and voltage-dependent Ca 2+ channels. Although bacterial cells do not have complex subcompartments or organelles, there is strong evidence that Ca 2+ plays an essential role in bacterial signaling, communication and stability similar to that observed in eukaryotic cells (Figure 1 (a)) [7] [8] [9] [10] [11] . Bacterial cells also have a well-regulated cytosolic free Ca 2+ concentration (ap- Viruses avidly perturb the intracellular Ca 2+ signaling network to achieve their own demand. A number of viral proteins (oval shape) from different families of viruses disrupt Ca 2+ signaling by targeting various Ca 2+ signaling components. Adapted with permission from ref. [3, 6] .