Early life experience potently shapes brain function and adult behavior. The biological bases underlying these windows of plasticity are increasingly being resolved in the developing mouse neocortex. This talk will cover core concepts of "critical periods" across sensory systems (visual, auditory, cross-modal). Pioneering the use of a molecular/genetic approach, we revealed that specific GABA circuits orchestrate the functional and structural rewiring of neural networks during sensory cortical development. Consequently, shifting excitatory-inhibitory (E-I) circuit balance or lifting a variety of molecular 'brakes' enables plasticity even beyond the early critical period. Understanding these events offers novel biomarkers of maturational milestones and deeper insight into neurodevelopmental disorders and therapeutic strategies in humans.