Microphysiological systems (MPS) are technological platforms that recapitulate functional units of human organs in vitro. There is no general unanimity in the definition of MPS and several platforms have been described as MPS technologies. Among these, are spheroids, static co-cultures, static micro patterned technologies, organ on chips (OOC), multi-organs on chips and human on chips (HOC). In this white paper we define MPS as advanced systems over the classic bi-dimensional (2D) cultures by including some of the following aspects: a three-dimensional (3D) framework (commonly referred to as scaffold) based on biomaterials of natural or synthetic origin; a 3D structure; a microfluidic counterpart; sensors to monitor MPS behaviour; an appropriate apparatus for MPS stimulation (e.g., electrical, mechanical cues); primary or stem cell-derived cells. MPS permit the study of human physiology in an organ-specific context, and they can find application in several fields. For instance, MPS can 1) help to unravel phenomena involved in the regulation of disease onset and progression, 2) support the drug development pipeline, and 3) contribute to chemical risk assessment. MPS may overcome the limits associated with traditional animal models, that are often not enough predictive of the human reality. Moreover, MPS present clear advantages in terms of cost, time, and ethical issues if compared with in vivo models. MPS demonstrated to be superior also to traditional 2D static cell culture models, that are not able to accurately reconstitute the in vivo cellular micro environment, tissue micro-architecture, and physiological functionality. The final goal is to develop systems, which combine 3D tissue models and flow-mimetic conditions, to recapitulate in vitro the complexity of human patho-physiology, thus effectively reproducing human clinical responses to drugs, and other exogenous stimuli.