In the inaugural issue of the journal Nature Aging a research team led by aging expert Linda P. Fried, MD, MPH, dean of Columbia University Mailman School of Public Health, synthesizes converging evidence that the aging-related pathophysiology underpinning the clinical presentation of phenotypic frailty (termed as “physical frailty” here) is a state of lower functioning due to severe dysregulation of the complex dynamics in our bodies that maintains health and resilience. When severity passes a threshold, the clinical syndrome and its phenotype are diagnosable. This paper summarizes the evidence meeting criteria for physical frailty as a product of complex system dysregulation. This clinical syndrome is distinct from the cumulative-deficit-based frailty index of multimorbiditys.