Reelin, a glycoprotein of the extracellular matrix, has been the focus of several studies over the years, mostly for its role in cell migration. Here we report the role of this molecule and of its downstream pathways in post-mitotic neurons and how they contribute to neural circuit assembly, refinement and function. Accumulating evidence has pointed at a major role for Reelin in axonal guidance, synaptogenesis and dendritic spine formation. In particular new evidence points at a direct role in axonal targeting and refinement at the target site. In addition, recent advances highlight new functions of Reelin in the modulation of synaptic activity, plasticity and behavior and it directly regulates GABA receptors expression and stability. We discuss these findings in the context of neurodevelopmental disorders. Highlights  Reelin signaling is required for axonal targeting and refinement at the target site.  Reelin signaling regulates dendritogenesis and spine formation in mature neurons.  Reelin modulates GABA receptors expression and stability, pre-and-post-synaptically.  Reelin is important for hippocampal integrity, synaptic plasticity and behavior.