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Objectives: As a complex, polygenic trait, brain size has likely been influenced by a range of direct and indirect selection pressures for both cognitive and non‐cognitive functions and capabilities. It has been hypothesized that hominin brain expansion was, in part, a correlated response to selection acting on aerobic capacity (Raichlen & Polk, 2013). According to this hypothesis, selection for aerobic capacity increased the activity of various signaling molecules, including those involved in brain growth. One key molecule is brain‐derived neurotrophic factor (BDNF), a protein that regulates neuronal development, survival, and plasticity in mammals. This review updates, partially tests, and expands Raichlen and Polk's (2013) hypothesis by evaluating evidence for BDNF as a mediator of brain size. Discussion: We contend that selection for endurance capabilities in a hot climate favored changes to muscle composition, mitochondrial dynamics and increased energy budget through pathways involving regulation of PGC‐1α and MEF2 genes, both of which promote BDNF activity. In addition, the evolution of hairlessness and the skin's thermoregulatory response provide other molecular pathways that promote both BDNF activity and neurotransmitter synthesis. We discuss how these pathways contributed to the evolution of brain size and function in human evolution and propose avenues for future research. Our results support Raichlen and Polk's contention that selection for non‐cognitive functions has direct mechanistic linkages to the evolution of brain size in hominins. [ABSTRACT FROM AUTHOR]