Experimental data of vascular smooth muscle (VSM) cell Ca2+ signals obtained by means of radioactive labelling, optical and electron microscopy, as well as molecular biological methods, have long hinted that healthy signalling depends not on passive diffusion of messenger species within the cytosol, but rather on carefully orchestrated communication between organelles. In particular, it seems necessary that organellar membrane domains of a few hundred nanometres in extension be separated by a distance of only a few tens of nanometres in order for efficient molecular transport to occur. These membranous juxtapositions, the transporters localized therein, the intervening cytosol, and molecular species form an environment we refer to as cytoplasmic nanospaces. Due to their restricted volume, they take advantage of the intrinsic variability, or stochasticity, of quantities like concentration, channel open probability, transporter activity, and thermal motion to ensure proper cellular function. By their very nature, our experimental observations lack the quantitative character that would permit full understanding of processes underlying Ca2+ signalling at these scales. Realistic quantitative modelling is ultimately necessary to aid our understanding and is becoming an essential tool to accompany experimental investigation in the biophysics and physiology of VSM. Based on firm experimental foundations, we have developed accurate stochastic models, using state-of-the-art tools for microphysiological stochastic simulations. These combine the ability to reconstruct three dimensional nanospace geometrical features and incorporate transporter distributions and kinetics with sophisticated so-called random walk algorithms that faithfully mimic molecular motion on those geometries. We present results from two models. In one, we explore the nature of Na+ transients localized to plasma membrane-sarcoplasmic reticulum (SR) nanospaces and occurring upstream of the Na+/Ca2+ exchanger-mediated Ca2+ influx that causes contractile activation of VSM via asynchronous Ca2+ waves. In the second instance, we examine the possibility that focal Ca2+ release by a nicotinic acid adenosine dinucleotide phosphate (NAADP)-sensitive receptor channel in the lysosomes could trigger a Ca2+ wave when lysosomes and SR form a nanospace.