This article summarizes the current knowledge of response-to-intervention (RTI) models in preschool settings, with an emphasis on evaluating the strengths and weaknesses of our current research base. Particular attention is given to the unique challenges of high-risk preschool settings. Presently, sufficient empirical support exists to begin establishing tiered intervention systems and building teacher capacity. Lacking, however, are valid and reliable assessment tools and insufficiently trained personnel to support a data-based decision-model within high-risk preschools. We conclude that organizational development should focus on building teacher capacity, establishing high-quality classroom instruction, and planning for sustainable programs, with adoption of a full RTI service delivery model serving as a long-range aspirational goal.