Guardian Angels (GA) are future zero-power, intelligent, autonomous systems-of-systems featuring sensing, computation, and communication beyond human aptitudes. GA will assist humans from their infancy to old age in complex life situations and environments. Zero-power reflects system-of-systems ability to scavenge energy in dynamic environments by disruptive harvesting techniques. The project prepares zero-power technologies based on future energy-efficient technologies, heterogeneous design, and disruptive energy scavengers.Three zero-power generations of GAs are foreseen:•\tPhysical Guardian Angels are zero-power, on-body networks or implantable devices that monitor vital health signals and take appropriate actions to preserve human health.•\tEnvironmental Guardian Angels extend monitoring to dynamic environments, using disruptive scavengers, personalized data communication, and first "thinking" algorithms. They are personal assistants that protect their wearers from environment dangers.•\tEmotional Guardian Angels are intelligent personal companions with disruptive zero-power, manmachine interfaces deployed at large scale. They sense and communicate using non-verbal languages playing an important role in health, education, and security worldwide.This project addresses the following scientific challenges for energy-efficient visionary Guardian Angel autonomous systems: (i) energy-efficient computing (down to E=10-100kT), (ii) and communication (approaching the limit of 1pJ/bit), (iii) low-power sensing, (iv) disruptive scavenging (bio-inspired, thermoelectric, etc, targeting energy densities of tens of mW/cm2), and (v) zero-power man-machine interfaces. A selection of emerging technologies based on energy efficiency is proposed. We will also develop design tools that integrate electrical, mechanical, optical, thermal, and chemical simulation tools over length and time scales currently not achievable.