The immune system is a source of regulation of the human body and is key for its stable functioning. Animal models have been successfully used for many years to study human immunity and diseases and provided significant contributions to the development of powerful new therapies. However, such models inevitably display differences from the human metabolism and disease state and therefore may correlate poorly with the human conditions. This explains the interest for the use of in vitro models of human cells, which have better potential to assist in understanding the physiological events that characterize the immune response in humans. Microfluidic technologies offer great capabilities to create miniaturized in vivo-like physiological models that mimic tissue-tissue interactions and simulate the body metabolism in both the healthy and diseased states. The micro-scale features of these microfluidic systems allow positioning heterogeneous cellular cultures in close proximity to each other in a dynamic fluidic environment, thereby allowing efficient cell-cell interactions and effectively narrowing the gap between in vivo and in vitro conditions. Due to the relative simplicity of these systems, compared to animal models, it becomes possible to investigate cell signaling by monitoring the metabolites transported from one tissue to another in real time. This allows studying detailed physiological events and in consequence understanding the influence of metabolites on a specific tissue/organ function as well as on the healthy/diseased state modulation. Numerous in vitro models of human organs have been developed during the last few years, aiming to mimic as closely as possible the in vivo characteristics of such organs. This technology is still in its infancy, but is promised a bright future in industrial and medical applications. Here we review the recent literature, in which functional microphysiological models have been developed to mimic tissues and to explore multi-tissue interactions, focusing in particular on the study of immune reactions, inflammation and the development of diseases. Also, an outlook on the opportunities and issues for further translational development of functional in vitro models in immunology will be presented.