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Introduction: A long-term stay of humans in space causes health problems and changes in protists and plants. Deep space exploration will increase the time humans or rodents will spend in microgravity (µ g ). Moreover, they are exposed to cosmic radiation, hypodynamia, and isolation. OMICS investigations will increase our knowledge of the underlying mechanisms of µ g -induced alterations in vivo and in vitro ., Areas Covered: We summarize the findings over the recent 3 years on µ g -induced changes in the proteome of protists, plants, rodent, and human cells. Considering the thematic orientation of microgravity-related publications in that time frame, we focus on medicine-associated findings, such as the µ g -induced antibiotic resistance of bacteria, the myocardial consequences of µ g -induced calpain activation, and the role of MMP13 in osteoarthritis. All these point to the fact that µ g is an extreme stressor that could not be evolutionarily addressed on Earth., Expert Opinion: In conclusion, when interpreting µ g -experiments, the direct, mostly unspecific stress response, must be distinguished from specific µ g -effects. For this reason, recent studies often do not consider single protein findings but place them in the context of protein-protein interactions. This enables an estimation of functional relationships, especially if these are supported by epigenetic and transcriptional data (multi-omics).