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Alternative education settings (AES; i.e., self-contained alternative schools, therapeutic day treatment and residential schools, and juvenile corrections schools) serve youth with complicated and often serious academic and behavioral needs. The use of evidence-based practices (EBPs) and practices with Best Available Evidence are necessary to increase the likelihood of long-term success for these youth. In this chapter, we define three primary categories of AES and review what we know about the characteristics of youth in these schools. Next, we discuss the current emphasis on identifying and implementing EBPs with regard to both academic interventions (i.e., reading and mathematics) and interventions addressing student behavior. In particular, we consider implementation in AES, where there are often high percentages of youth requiring special education services and who have a significant need for EBPs to succeed academically, behaviorally, and in their transition to adulthood. We focus our discussion on: (a) examining approaches to identifying EBPs; (b) providing a brief review of EBPs and Best Available Evidence in the areas of mathematics, reading, and interventions addressing student behavior for youth in AES; (c) delineating key implementation challenges in AES; and (d) providing recommendations for how to facilitate the use of EBPs in AES.