There is increasing consensus that disruptive behavior disorders and syndromes (DBDs) are identifiable in preschool children. There is also concomitant recognition of the limitations of the current DBD nosology for distinguishing disruptive behavior symptoms from the normative misbehavior of early childhood. In particular, there appears to be substantial insensitivity to heterotypic manifestations of this developmental period and problems in identifying meaningful heterogeneity. As a result, the developmental basis for much of the current nosology may be called into question. To address these and other critical issues, this paper reviews the foundational elements of clinical and developmental science pertinent to developmental differentiation of disruptive behavior in the preschool period as paradigmatic for developmental specification across the lifespan and generates an agenda for future research. We begin by reviewing evidence of the validity of DBDs in preschool children. This is followed by an outline of key developmental concepts and a review of the corollary evidence from developmental science. These provide a basis for conceptualizing disruptive behavior in reference to developmental deviation in four core dimensions hypothesized to mark the core features of disruptive behavior syndromes. Finally, we propose a program of research to establish an empirical basis for determining the incremental utility of a developmentally specified nosology. Central to this approach is a contention that the benefits of developmental specification are extensive and outweigh any disadvantages. This is because a developmentally specified approach holds substantial promise for increasing sensitivity and specificity for differentiating disruptive behavior from normative misbehavior and from other related syndromes as well as for improving prediction. Further, more precisely defined, developmentally based phenotypes are likely to elucidate distinct mechanisms within translational studies and to serve as a catalyst for the generation of novel treatments.