The idea that serious mental illnesses such as autism and schizophrenia result from abnormal connectivity of large-scale brain networks is gaining widespread acceptance. Efforts to test dysconnectivity hypotheses have historically been hindered by tools with insufficient spatial resolution to investigate human brain connectivity in vivo and an incomplete understanding of the large-scale organization of the brain, the so called “connectome.” The development of resting-state functional connectivity MRI (rs-fcMRI) has profoundly affected our understanding of the functional organization of the brain, both in health and illness. The investigation by Cerliani and coauthors in this issue reports abnormal cortical-subcortical connectivity in autism1. In this editorial, we briefly review rs-fcMRI methods, summarize several key rs-fcMRI findings in two exemplary dysconnectivity psychiatric illnesses, schizophrenia and autism, and discuss the potential usefulness of rs-fMRI in the search for biomarkers of psychiatric disorders.