Resilience or vulnerability to stress-related emotional disorders is governed in part by early-life experiences. Early-life adversity can profoundly impact an individual’s risk for depression, likely by modulating the maturation of the underlying brain circuits. Microglia, the brain’s resident immune cells, have emerged as key effectors in the shaping of synaptic connectivity in the developing visual and other sensory systems. In this talk, I will present evidence that microglia play a similar role in sculpting connectivity of stress-related hypothalamic neurons. My data demonstrate that microglia are likely contributors to early-life experience-dependent synaptic rewiring of stress-sensitive neurons, and manipulation of microglial function during development may prevent stress-related emotional disorders in adulthood, thereby providing novel targets for therapeutics or preventative interventions in at-risk children.