© 2021 by the authors., Insulin-like growth factor 1 (IGF-1) is a peptide hormone belonging to the insulin family of proteins. Almost all of the biological effects of IGF-1 are mediated through binding to its high-affinity tyrosine kinase receptor (IGF1R), a transmembrane receptor belonging to the insulin receptor family. Factors, receptors and IGF-binding proteins form the IGF system, which has multiple roles in mammalian development, adult tissue homeostasis, and aging. Consequently, mutations in genes of the IGF system, including downstream intracellular targets, underlie multiple common pathologies and are associated with multiple rare human diseases. Here we review the contribution of the IGF system to our understanding of the molecular and genetic basis of human hearing loss by describing, (i) the expression patterns of the IGF system in the mammalian inner ear; (ii) downstream signaling of IGF-1 in the hearing organ; (iii) mouse mutations in the IGF system, including upstream regulators and downstream targets of IGF-1 that inform cochlear pathophysiology; and (iv) human mutations in these genes causing hearing loss., This research was funded by Spanish FEDER/CM, B2017/BMD-3688; FEDER/MICIN, PID2020-115274RB-I00-THEARPY and EU H2020-INTERREG, 0551_PSL_6_E grants to I.V.-N. and ACCI/ISCIII, ER19P5AC761 grant to L.R.-d.l.R. Á.G.-M. holds a FPU (FPU16/03308; MECD) contract. S.M.-C. and L.R.-d.l.R. hold CIBER ISCIII researcher contracts.