Abstract The microcirculation exemplifies the mesoscale in physiological systems, bridging larger and smaller scale phenomena. Microcirculatory research represents an example of a ‘middle‐out,’ rather than ‘top‐down’ or ‘bottom‐up,’ approach to the study of biological function. Computational and mathematical approaches can be used to analyse the functioning of the microcirculation and to establish quantitative relationships between microvascular processes and phenomena occurring on larger and smaller scales, leading to insights which could not be obtained solely by reductionist biological experiments. Given its integrative approach to processes occurring on disparate scales and its emphasis on theoretical as well as experimental approaches, microcirculatory research belongs within current definitions of systems biology.