New advances in neurobiology are revealing that brain development and the learning it enables are directly dependent on social-emotional experience. Growing bodies of research reveal the importance of socially-triggered epigenetic contributions to brain development and brain network configuration, with implications for social-emotional functioning, cognition, motivation and learning. Brain development is also impacted by health-related and physical developmental factors, such as sleep, toxin exposure, and puberty, which in turn influence social-emotional functioning and cognition. An appreciation of the dynamic interdependencies of social-emotional experience, health-related factors, brain development and learning underscores the importance of a “whole child” approach to education reform, and leads to important insights for research on Social-Emotional Learning (SEL). To facilitate these interdisciplinary conversations, here we conceptualize within a developmental framework current evidence on the fundamental and ubiquitous biological constraints and affordances undergirding SEL-related constructs and learning more broadly. Learning indeed depends on how nature is nurtured.