The formation and function of the mammalian cerebral cortex relies on the complex interplay of a variety of genetic and environmental factors through protracted periods of gestational and postnatal development. Biogenic amine systems are important neuromodulators, both in the adult nervous system, and during critical epochs of brain development. Abnormalities in developmental programming likely contribute to developmental delays and multiple neurological and psychiatric disorders, often with symptom onset much later than the actual induction of pathology. We review several genetic and pharmacological models of dopamine, norepinephrine and serotonin modulation during development, each of which produces permanent changes in cerebral cortical structure and function. These models clearly illustrate the ability of these neurotransmitters to function beyond their classic roles and show their involvement in the development and modulation of fine brain circuitry that is sensitive to numerous effectors. Furthermore, these studies demonstrate the need to consider not only gene by environment interactions, but also gene by environment by developmental time interactions.