Children with 22q11.2 deletion syndrome exhibit high rates of social-behavioral problems, particularly in the internalizing domain, indicating an area in need of intervention. The current investigation was designed to obtain information regarding parent and teacher ratings of the social-emotional behavior of children with 22q11DS. Using the Child Behavior Checklist (CBCL), the sample included 67 children with 22q11DS and 59 control subjects. Results indicated significant differences in social-behavioral functioning of children with 22q11DS, as compared to a control group, based on rater type. Specifically, parents reported more difficulties with internalizing problems, withdrawal, and social problems in children with 22q11DS. In contrast, teachers perceived few differences between children with 22q11DS and unaffected children. Correlational analyses indicated weak concordance between parent and teacher reports, with no significant correlations on any of three summary scales. The findings support the use of multiple methods of assessment and multiple informants when collecting information regarding the social-behavioral functioning of children with 22q11DS, and that interpretations based on only one informant/setting need to be made cautiously.