Frailty is a multisystem syndrome of decreased physiologic reserve that has been shown to strongly and independently predict morbidity and mortality. Frailty is prevalent in patients living with kidney disease and occurs earlier in individuals with kidney disease as compared to the general population. In this comprehensive review, we examine clinical and research applications of frailty in kidney disease populations. Specifically, we clarify the definition of frailty and address common misconceptions, review the mechanisms and epidemiology of frailty in kidney disease, discuss challenges and limitations in frailty measurement, and provide updated evidence related to risk factors for frailty, its associated adverse outcomes, and interventions.