This talk underscores bidirectional links between real-world driving behavior in health and disease, along with promising evidence-based measures and effective configurations of sensor technologies for recovering health-relevant data from human behavior and the “brain-in-the wild”. Our research teams use human factors/ergonomics, ethology, systems thinking, and novel tools to synchronize sensor signals and glean digital biomarkers from continuous decades of big, real-world data from a person’s own environment–at home, at work, at play, and in transit– to answer fundamental questions translatable to clinical research and practice. Our work, supported by the US NIH and industry, underscores the most promising evidence-based measures and effective configurations of sensor technologies for recovering health-relevant data in the real world. We have extended this data collection to automobile driving, in line with the NIH “All of Us” efforts to collect prospective data from up to a million people in the field. In our work, a person’s own car and ubiquitous personal sensors capture a wide variety of health data, paving the way for egalitarian access to healthcare diagnostics outside the traditional confines of a hospital, clinic or workplace. The results can then be confidentially shared with medical practitioners and researchers through the electronic medical record to address a range of medical disorders such as diabetes and arthritis, visual and mental disorders, aging, and neurodegenerative disorders such as Alzheimer’s and Parkinson’s diseases –that affect perception, attention, cognition, sleep, mobility, and mood, the fundamental quotidian determinants of human behavior. These efforts require innovative multidisciplinary team science, novel sensor-technologies, experimental designs, bioinformatics, analytic approaches to observational data, computer vision and machine learning tools, and close attention to personal privacy rules and ethics. This approach may also meet urgent societal needs, as expressed by the US NIH and FDA, to track post-acute sequelae of the SARS-CoV-2/ COVID-19 pandemic and to track the efficacy of drugs, biological agents and devices in the real world. Ongoing developments underscore the promise of public and private investment in neuroscience research – and the need for federal regulators to be prepared to address unique technologies and diagnostic modalities as they continue to emerge.