Across a range of mammalian species, early developmental variations in fear-related behaviors constrain patterns of anxious behavior throughout life. Individual differences in anxiety among rodents and non-human primates have been shown to reflect early-life influences of genes and the environment on brain circuitry. However, in humans, the manner in which genes and the environment developmentally shape individual differences in anxiety and associated brain circuitry remains poorly specified. The current review presents a conceptual framework that facilitates clinical research examining developmental influences on brain circuitry and anxiety. Research using threat-exposure paradigms might most directly integrate basic and clinical perspectives on pediatric anxiety.