Social cognitive neuroscience is a novel field of interdisciplinary research that examines socio-emotional cognition and behavior by emphasizing the neural substrates of these processes. Insights from this biological perspective have established that socio-emotional processing does not happen in a sequential order but in a recursive and interlinked fashion; that individual brain regions are not associated with one, but multiple, distinct social functions; and that brain regions are organized into dynamically interacting networks. These factors explain why it is difficult to pinpoint the neural substrates of particular social deficits in patients with brain diseases. With that said, there are specific brain regions that are highly specialized for the perception, regulation, and modulation of emotion and behavior. This article will review key aspects of social processing beginning with their underlying neural substrates, including (1) perception of social signals, (2) social and emotional evaluation, and (3) behavioral response generation and selection. Case studies will be used to illustrate the real-life social deficits resulting from distinct patterns of neuroanatomic damage, highlighting the brain regions most critical for adequate social behavior. Continuum Lifelong Learning Neurol 2010;16(4):69-85.