Interlinked and fundamental aging processes appear to be a root-cause contributor to many disorders and diseases. One such process is cellular senescence, which entails a state of cell cycle arrest in response to damaging stimuli. Senescent cells can arise throughout the lifespan and, if persistent, can have deleterious effects on tissue function due to the many proteins they secrete. In preclinical models, interventions targeting those senescent cells that are persistent and cause tissue damage have been shown to delay, prevent or alleviate multiple disorders. In line with this, the discovery of small-molecule senolytic drugs that selectively clear senescent cells has led to promising strategies for preventing or treating multiple diseases and age-related conditions in humans. In this Review, we outline the rationale for senescent cells as a therapeutic target for disorders across the lifespan and discuss the most promising strategies-including recent and ongoing clinical trials-for translating small-molecule senolytics and other senescence-targeting interventions into clinical use.