Schools are being confronted with an increasing population of high-functioning students with autism spectrum disorder (HFASD). These students pose particular challenges to school-based practitioners and teachers given their social-communication deficits, restricted and repetitive behaviors/interests, and relative cognitive and language strengths. This article examines the impact of HFASD at the student, classroom, and district levels, and existing evidence-based strategies and techniques to improve social competence and daily functioning. It then proposes a comprehensive intervention framework for school practitioners and provides an example of a model comprehensive school-based program. Future directions and areas in need of study are also discussed.