Frailty is a clinical condition characterized by a decrease of reserves and functions across multiple physiological systems, responsible for a compromised ability to cope with stressors [1]. Frailty is highly prevalent in older persons [2,3], and is associated with a higher risk of adverse outcomes (including death, falls, fractures, hospitalization, and disability) [1,4,5]. It is, thus, evident why it is increasingly considered an important public health problem. In this special issue, we present a set of articles spanning over different aspects of frailty research, from its definition and measurement, to the identification of risk factors and promising biomarkers, up to ad hoc interventions and treatment.