Calcium and its ubiquitous intracellular receptor calmodulin are required for cell proliferation. Studies in a variety of model systems are beginning to identify components of the calcium/calmodulin cascade required for movement of quiescent cells into the cell cycle as well as for proliferating cells to move from G1 to S, G2 to M and through mitosis. Two calcium/calmodulin-dependent enzymes, the multifunctional calcium/calmodulin-dependent protein kinase and the protein phosphatase 2B (calcineurin) as well as a spindle pole body protein that binds calmodulin in the absence of calcium have been shown to be essential at specific phases of the cell cycle. In addition, the status of the intracellular calcium pools is critical for normal traverse of the cell cycle.