Frailty is a public health issue that is experienced by homeless and other vulnerable populations; to date, a frailty framework has not been proposed to guide researchers who study hard-to-reach populations. The Frailty Framework among Vulnerable Populations has been developed from empirical research and consultation with frailty experts in an effort to characterize antecedents, that is, situational, health-related, behavioral, resource, biological, and environmental factors that contribute to physical, psychological, and social frailty domains and impact adverse outcomes. As vulnerable populations continue to age, a greater understanding of frailty will enable the development of nursing interventions.