Maturing neural circuits are dramatically shaped by the environment, but this timing varies across brain regions and plasticity declines with age. Focusing on cellular/molecular mechanisms underlying these developmental trajectories, this lecture explores specific events controlling the onset and closure of such ‘critical periods’. The dynamic balance of emerging excitatory-inhibitory (E/I) circuitry triggers plasticity. Targeting particular GABA circuits by pharmacological or genetic manipulations can either accelerate or delay critical period onset. Instead, plasticity appears to wind down as brake-like molecular factors emerge to stabilize adult networks. Lifting these brakes reopens windows of circuit rewiring, carrying broad implications for understanding the etiology and potential therapeutic strategies toward neurodevelopmental disorders or recovery from brain injury in adulthood.