In the past decade, much progress has been made towards understanding how neurons, the cells responsible for the processing and transfer of information in the central nervous system (CNS), interact with non-neuronal brain cells. However, there is still a lack of information about how non-neuronal cells contribute to the structural and functional maturation of the neuronal junctions known as synapses. Our work focuses on identifying and elaborating the genes, molecules, and signaling pathways that are crucial for linking non-neuronal cells with the synaptic structures that have been shown to be severely disrupted in nearly all known neurodevelopmental and psychiatric disorders. The long-term goal of our research is to contribute to novel therapeutic strategies to prevent or repair the impaired synaptic connectivity that occurs during abnormal brain development and following CNS injury or insult. My previous findings led me to postulate that the formation and maturation of synapses and dendritic spines, the mushroom-like protrusions that receive excitatory synaptic contact, are not entirely neuron-intrinsic processes. Using a wide array of techniques including transgenic mouse lines, in vitro and ex vivo culture systems, and three-dimensional reconstructions of spines and synapses in the mouse brain at the highest level of resolution, I have determined that multiple stages of synaptic development are highly regulated by astrocytes, the most abundant glial cell type in the brain. Going forward, I believe that understanding the complex relationships between astrocytes, spines, and synapses will be key to forging new therapies for brain disorders characterized by aberrant synaptic connectivity, including autism, schizophrenia, and addiction.