Predictive Health Management (PHM), originally applied in the Aerospace Industry, tries to predict when what part would fail for what reason(s) in order to make preventive maintenance more efficient and cost-effective. Over the past several years, PHM has been infused increasingly into the human healthcare, precision medicine, and human performance sectors. As such, a diverse and trans-disciplinary group of expert authors presents in this Special Issue on PHM for Human Health & Performance its perspectives on PHM in the context of prognostics and health management for human health and performance, both on Earth and in space, in nine excellent contributions that cover a wide range of current research and application topics related to this emerging field. In particular, these contributions highlight various technological and analytical aspects that in combination contribute and make a reality an autonomous healthcare paradigm. These aspects include, but are not limited to: wearable smart sensors, rehabilitation devices and robotics, image classification, signal processing, data mining, data understanding, machine learning, prediction and diagnosis, electronic health records and databases, and overarching PHM-based healthcare frameworks, etc.