Insulin-like growth factor I (IGF-I) is an important component of the somatotropic axis and has been evaluated as an indicator trait for livestock improvement. This review synthesizes findings from a long-term divergent-selection experiment initiated in Angus cattle at The Ohio State University in 1989, with related records collected through 2017. Selection produced substantial divergence in serum IGF-I concentration, and subsequent analyses confirmed moderate heritability and persistent additive genetic variation. Although selection successfully altered circulating IGF-I concentration, neither the high nor low line consistently exhibited a favorable combination of economically important traits. Correlated responses in body weight, growth, skeletal development, feed efficiency, carcass composition, and reproduction were generally modest, heterogeneous, and dependent on age, sex, diet, trait definition, and analytical approach. Candidate variants in IGF1, GH, GHR, IGF2, and PIT1 were associated with variation in IGF-I and related phenotypes, but no single locus accounted for the long-term selection response. Likewise, serum IGF-I concentration diverged without corresponding divergence in circulating IGF-binding proteins. The results support a complex, polygenic, and context-dependent model of IGF-I regulation. Serum IGF-I is therefore most appropriately considered an intermediate phenotype within a multi-trait breeding framework rather than a stand-alone selection criterion.