The multiplicity of mechanisms involved in regulation calcium (Ca2+) dynamics, the non-homogenous spatial distribution of cellular components and the presence of microdomains in vascular cells (smooth muscle (SMC) and endothelial cells (EC) ) result in both intra- and intercellular heterogeneities in Ca2+ levels inside the cells. Experimentation has revealed variety of these intricate intra- and inter-cellular Ca2+ spatiotemporal patterns. The mechanisms behind them remain unresolved. Different variants of deterministic and stochastic models have been proposed to explain global events like Ca2+ oscillations, waves and local events such as Ca2+ sparks and puffs. However, these models are rarely tissue specific and have not been integrated with other important intra- and inter-cellular signaling pathways. Here, we describe the development of detailed computational models that investigate vascular signaling and microcirculatory function. We have previously developed and validated “well-mixed” models of Ca2+ and plasma membrane Vm dynamics in EC and SMC from rat mesenteric arterioles. Models are integrated into multicellular arrangements and adapted to incorporate intra-cellular spatial heterogeneities of cellular components and microdomains like myoendothelial projections. Localized EC Ca2+ mobilization is induced in EC during SM stimulation in the presence of myoendothelial projections which enables an endothelial feedback response that moderates SMC constriction. Myoendotheial IP3 ¬diffusion is more likely than Ca2+ to mediate this response. Spatial distribution of store or membrane receptor distribution was essential for reproducing intracellular Ca2+ waves in both EC and SMC. Ca2+ diffusion synchronized localized oscillators to form an oscillatory Ca2+ wave. Voltage operated Ca2+ channels modulate Vm oscillations and regulate Ca2+ wave velocity and transition to whole cell oscillations. Electrical current through gap junctions (carried predominantly by K+ ions) is the primary signal that enables conducted responses. Intercellular Ca2+ and IP3 fluxes are small and thus, their passive diffusion is predicted to have a limited effect on Ca2+ mobilization at distant cells. These weak fluxes may be adequate, however, to amplify local current in conducted responses and to promote synchronization of whole cell oscillations of neighboring SMCs in vasomotion. Mathematical models of Ca2+ and Vm dynamics in endothelial and smooth muscle cells allow a more comprehensive investigation of intra and inter-cellular Ca2+ signaling and the elucidation of mechanisms behind localized and global Ca2+ events in the vascular cells.