This chapter reviews imaging studies delineating the unique neuropsychiatric features of Williams-Beuren syndrome (WS), as well as recent advances in investigating the neural substrates of the disorder, which have provided significant contributions to unraveling the impact of a specific genetic defect on brain structure and function. It discusses the clinical, behavioral, cognitive and genetic profiles of WS. Studies using high-resolution magnetic resonance imaging (MRI) have found significant brain differences between WS and typically developing individuals. Significant advances in the understanding of the structural basis of WS have come from the application of voxel-based morphometry (VBM), which allows the study of genetic variation without restriction to anatomical boundaries. Findings of the studies reviewed in the chapter offer a systems-level characterization of genetically mediated abnormalities of neural interactions that can be probed for the identification of single-gene effects on brain maturation.