The study of behavioral phenotypes associated with genetic syndromes has gained increasing momentum over the past two decades. In this paper, the definition of behavioral phenotypes is presented and the complexities and obstacles to progress in this field are summarized. Also described are the goals of such investigations, including the need for syndrome delineation, provision of guidance for clinical management, contributions to understanding brain-behavior relations, advancements in developmental theory, and gaining understanding of the genetic bases of behavior. Methodological issues addressed in relation to such goals include the need for cross-disciplinary collaboration, concerns regarding sampling methods and comparison group selection, and developmental considerations. The complexity of cognitive abilities, the limitations of existing tests and measures, and ways of approaching the study of behavior are discussed. A final comment concerns the potential risks of research in behavioral phenotypes.