Since the conception of the Education for All Handicapped Children Act in 1975 there has been substantial progress regarding the education of learners with disabilities. Nevertheless, significant challenges remain for addressing the diverse needs of these learners and improving in- and out-of-school outcomes. This special issue focuses on an approach that holds promise for the delivery of interventions that are aligned to learners' social, emotional, behavioral, and learning needs - multi-tiered systems of support (MTSS). The four articles that comprise the special issue highlight the need for actionable information for schools implementing MTSS, early intervention for children with or at risk for disabilities, and an enhanced focus on intensive interventions. This introduction to the special issue provides information on the meeting that motivated the special issue, a summary of each of the four articles, and paths forward for early and sustained intervention for learners with or at risk for disabilities.