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Background: Longitudinal bone growth is regulated by multiple endocrine signals (e.g., growth hormone, insulin-like growth factor I, estrogen, and androgen) and local factors (e.g., fibroblast growth factors and their receptors and the C-natriuretic peptide/natriuretic peptide receptor-B pathway)., Summary: Abnormalities in both endocrine and local regulation of growth plate physiology cause many disorders of human skeletal growth. Knowledge of these pathways creates therapeutic potential for sustaining or even augmenting linear growth. Key Message: During the past 4 decades, advances in understanding growth plate physiology have been accompanied by development and implementation of growth-promoting treatments that have progressed in both efficacy and specificity of action. This paper reviews the history and continuing evolution of growth plate therapeutics., (© 2021 S. Karger AG, Basel.)