We provide an overview of the role professional development plays in multitiered prevention and intervention models. Specifically, professional development is discussed within the context of establishing sustainable improvement in schools as professionals implement multitiered models of prevention and intervention services, programs, and practices related to response to intervention. We discuss the system capacity for sustainable improvement and system-wide procedures that can be implemented to support multitiered prevention models. We also discuss various models, levels of professional development, and the relationship between professional development implementation and sustainability of school improvement. We conclude with a discussion of the challenges schools are likely to face in establishing response to intervention. We also note what preservice and in-service professional development activities can offer to help overcome some of these challenges and barriers to system-wide change in quality prevention and intervention programs. (Contains 4 tables.)