BACKGROUND: Orthopedic diseases, including osteoarthritis, osteoporosis, and age-related musculoskeletal disorders, significantly impact quality of life and are becoming increasingly prevalent with aging populations. A growing body of evidence highlights the role of cellular senescence in the pathogenesis of these conditions. Senescent cells (SCs), characterized by irreversible cell cycle arrest, accumulate in tissues over time, contributing to inflammation, tissue degeneration, and impaired regeneration. The emerging field of senolytics, which aims to selectively eliminate these SCs, has garnered attention as a novel therapeutic strategy in orthopedics. SUMMARY: Senolytic drugs, including small molecules, peptides, and natural compounds, have shown promise in preclinical models and early clinical trials for the treatment of various age-related diseases. In orthopedics, senolytics have been investigated for their potential to ameliorate cartilage degradation, bone fragility, and other degenerative changes associated with aging. Recent studies have demonstrated that targeting SCs in musculoskeletal tissues can improve tissue function, reduce inflammation, and promote regeneration. Although the majority of research is still in the preclinical phase, the positive outcomes from animal studies and early clinical trials suggest that senolytic drugs may offer new therapeutic avenues for orthopedic diseases. KEY MESSAGES: Senolytic therapies hold significant potential for treating orthopedic diseases by targeting the underlying cellular senescence that contributes to tissue degeneration and inflammation. Preclinical and clinical studies indicate that senolytic drugs may enhance tissue repair, alleviate symptoms, and slow disease progression in musculoskeletal disorders. Further research is needed to optimize drug efficacy, ensure safety, and identify patient populations that may benefit the most from these treatments. The development of senolytic drugs could revolutionize the management of aging-related orthopedic diseases, providing a more targeted and effective approach than current treatments.