Microphysiological systems (MPS, also known as ‘organ-on-a-chip’, ‘body-on-a-chip’, or ‘human-on-a-chip’) have emerged over the last fifteen years as attractive systems to probe response to pharmaceutical or chemicals. While applicable to animals, such systems are particularly powerful in predicting human response prior to clinical testing of a drug or as augmentation of clinical studies to test underlying mechanisms. The rate of development of such systems has increased exponentially, particularly over the last three years. Organ-on-a-chip systems have evolved in sophistication and ability to model details of organ physiology, allowing better understanding of underlying mechanisms of response to drugs and chemicals. Body-on-a-chip (BOC) systems are multi-organ systems, often designed to emulate human physiological response to drugs and have the potential to capture both efficacy of a drug and potential toxicity in other organs. While the focus has been on human response to pharmaceuticals, such systems can evaluate response to general chemical exposure, which is important in evaluating the safety of chemicals, food ingredients, and cosmetics. Here, we review recent progresses in the development of model systems over the last three years, with particular focus on BOC systems. The physiological relevance of the model systems is a key factor that determines the success of drug development.1 Although animal models have been the gold standards for preclinical drug testing, animal models often do not predict human response effectively,2 increasing the demand for more advanced model platforms. In addition to the high cost and the ethical issues associated with using animal models, accurate extrapolation of data from animal experiments to humans is also an important limitation. In vitro cell-based models with a single cell type in static culture require lower cost and are more adaptable to high-throughput format but cannot recapitulate many of the complex biological phenomena as well as BOC systems. Microphysiological systems (MPS) offer several advantages, such as recapitulation of tissue architecture, diffusion kinetics of drugs and signaling factors, and physiological flow conditions.3 Since the initial development in early 2000s, various organ-on-a-chip (OOC) devices have been developed, some of them showing notable successes in recapitulating the physiological functions of in vivo tissues, which was not possible using traditional cell culture models.4 One of the fundamental issues with current cell-based single tissue/organ in vitro models is that they cannot reproduce complex interactions between different organs or tissues in the body. This can be a critical issue, since such interactions in the body play essential roles in maintaining homeostasis, as well as in many cases of pathologies. Traditional cell culture models or current OOC systems targeting a single organ or tissue cannot achieve this level of complexity. Such a limitation of traditional in vitro models becomes more critical when dealing with complex pathologies, such as metabolic diseases, obesity, and immunological disorders. MPS technology, which relies heavily on microfabrication and microfluidics, is ideal for mimicking such interactions in a reductionist way, by connecting and integrating multiple ‘modules’ of OOC systems.5 These multi-organ systems are often termed as BOC, human-on-a-chip, multi-organ microphysiological systems (MOM), or multi-organ-on-a-chip (MOC), and have emerged as potential tools to evaluate both a drug’s efficacy and side effects that may limit the drug’s usefulness. BOC systems are constructed to mimic the physiological ratios of organ sizes and flow,6 while MOC systems may not necessarily attempt to emulate physiological conditions. Proof-of-concept studies of multi-organ systems were first reported almost 15 years ago,7–9 and were used to understand the mechanism of toxicity of naphthalene in rodents and to explain differences in response of rats and mice to naphthalene. Since then, recent advances in MPS systems, organoids and stem cell technology, and in vitro vascularization techniques have contributed to the development of improved BOC systems. In this review, we highlight recent progresses in MPS systems aimed at reproducing multi-organ physiology of the human body. We discuss recent advances in novel microfluidic platforms that connect multiple organ modules, and on-chip sensing techniques for real-time analysis of BOC systems, and BOC systems aimed at modeling diseases and drug testing. As described in this review, we have seen remarkable developments in BOC systems. Overcoming several existing challenges promises more advanced systems that can be potentially applicable to clinical situations or incorporated into the drug development process. We will review first advances in the microfluidic platforms for BOCs, then techniques, particularly on-chip systems to monitor responses, then selected single organ systems with multiple cell types, then devices with multiple interacting organ modules.