Over the past 25 years, our understanding of the risks conferred by “behavioral inhibition to the unfamiliar” (BI) has grown tremendously, yet many questions remain. BI represents the persistent tendency to show extreme reticence, fearfulness, or avoidance in novel situations or with unfamiliar people. Prospective studies of high-risk offspring, selected community children, and unselected epidemiologic samples converge to suggest that BI confers specific risk for social anxiety disorder in early and middle childhood and adolescence. Later outcomes are less clear, with some studies suggesting associations with depression or panic disorder. Studies that find broad associations between BI and anxiety proneness in general may be limited by the absence of information about parental psychopathology (an important potential confound associated with both BI and anxiety disorders in offspring). A critical area for further inquiry is the degree to which BI confers risk for social anxiety disorder in the absence of family history of anxiety disorders. Additionally, although progress has been made in identifying risk factors, protective factors, and treatments that may influence the course of BI and associated anxiety, more work is needed. Also, several exciting inroads have been made into the genetic and neurobiologic underpinnings of BI, and future studies promise greater elucidation of these areas. For now, the clinical take-home message is that preschool-age children presenting with extreme and persistent BI are at elevated risk for social anxiety disorder and possibly for other future disorders; preliminary evidence suggests that these children may be helped by early cognitive-behavioral intervention. Depression and Anxiety 25:357–367, 2008. © 2008 Wiley-Liss, Inc.