In this issue, Varadhan and colleagues propose a methodologic framework that seeks to quantify impaired resiliency in dynamic systems underlying the frailty syndrome. We view this work, which is based on modeling stimulus-response data, as an exciting expansion of longstanding theories of age-related decline in physiologic reserve across systems. We outline ways in which this methodology might make substantial contributions in frailty research and clinical practice, and we discuss potential obstacles in its operationalization.