The functions of biological systems are, whether one considers events occurring within a single cell or between cells in a multicellular tissue setting, controlled by the integration of many different molecular pathways. This is pertinent to our understanding of vascular function: one often studies individual smooth muscle or endothelial cells in isolation or in a heterocellular blood vessel segment. In particular, it is clear that cellular processes are finitely regulated in both time and space evincing the need to consider the complexity of this spatiotemporal signalling. Much attention over the last decade has been given to the possibility that caveolae act as signalling centres to orchestrate important spatiotemporal modalities in vascular cells and tissues. Caveolae are Ω-shaped plasmalemmal invaginations first observed in electron microscopy studies of the 1950s and they are prominent features of both smooth muscle and endothelial cells. Ultrastructural investigations informed the suggestions that these structures were somehow involved in regulating transfer of information from outside to the cell interior but molecular details were lacking. This was until the discovery of a molecule -caveolin-1 – that was essential for the formation of caveolae via its interactions with cholesterol. The subsequent ability to alter caveolin/caveolae function by altering cholesterol levels and/or knocking out caveolin gene expression accelerated our understanding of vascular cell spatiotemporal signalling. It quickly became apparent that caveolins (a family of proteins comprising three main isoforms) served important functions in signal orchestration. In endothelial cells they were found to be crucial to the dynamic regulation of eNOS activity, and thereby NO bioavailability, through the actions of a 20-amino acid peptide termed the scaffolding domain peptide (SDP) [1]. In smooth muscle cells, the SDP was also found to interfere with the ability of contractile stimulants to redistribute important intracellular signalling molecules [2]. The list of putative caveolin interacting partners is now extensive. With this reinvigoration of research into caveolae function, attention also turned to the possibility that these structures could regulate Ca2+ homeostasis and ion channel function. Use of cholesterol sequestering agents to ablate ultrastructural appearance of caveolae are now commonplace. Although one’s interpretations must be cautioned by the multiplicity of actions of such manoeuvres, they indicate that caveolae are important in the regulation of Ca2+ sparks and Ca2+ waves in vascular cells [3, 4], findings that have been supported by studies in cells isolated from caveolin knockout mice. Recent digitised 3-dimensional reconstructions of electron micrographs of vascular smooth muscle continue to highlight close associations of caveolae to the underlying sarcoplasmic reticulum, the latter being crucial to the genesis of Ca2+ sparks and waves. The influence of caveolae extends beyond the microscopic scale of single cells to the macroscopic tissue setting. Alteration of caveolin/caveolae results in changes in the capacity of blood vessels to contract and relax and caveolin/caveolae have now been implicated in altered vascular function (and structure?) in various pathophysiological conditions. A particular unexpected discovery has been that endothelial caveolae are important for the genesis of endothelium-derived hyperpolarising factor-mediated relaxations [5]. Many exciting challenges remain however. As the simpler questions have been answered (“are caveolae important components of vascular cell function?”) then more complex scenarios require elucidation. Are the extensive number of proposed molecular interactions with caveolin/caveolae possible in one vascular cell type? Also, how reasonable is it to generalise interpretations across different experimental scenarios – e.g. cholesterol sequestration, caveolin-deletion (knockout animals) and caveolin-depletion (RNAi knockdown) – albeit each are designed to investigate caveolae function? Many situations also remain to be resolved about the vascular role of each caveolin isoform and their contribution to adaptive functional changes. Are there caveolin-specific roles and are these altered in vessel-, gender-, stimulus- or disease-specific manners? And what of proteins other than caveolins that have also been identified as crucial for membrane invaginations showing morphological similarities to caveolae [6, 7]? How do they themselves control vascular function and do they do so in concert with caveolins? As in the last 10 or so years, so the next decade promises to uncover much new information about the roles of caveolae, and constituent molecules, in the spatiotemporal regulation of vascular function in physiological and pathophysiological circumstances.