Since its inception, the discipline of psychology has utilized empirical epistemology and mathematical methodologies to infer psychological functioning from direct observation. As new challenges and technological opportunities emerge, scientists are once again defining measurement paradigms for psychological health and illness to solve novel problems and capitalize on new technological opportunities. The current keynote discuss the theoretical foundations and scientific advances in remote sensor technology and machine learning models as they are applied to quantify psychological functioning and draw clinical inferences. We will present examples across different disorders and risk profiles including posttraumatic stress, depression, and suicide risk.