Using socio-ecological theory, this study explores best practice (educational practices correlated with higher student performance) in middle-school science. Seven schools with consistently higher student performance were compared with three demographically similar, average-performing schools. Best practice included instructional approaches (relevance and engagement, inquiry, differentiated instruction, collaborative work, moderate amounts of homework, and integration of language literacy and science) and administrative practices (nurturing a climate of opportunity to succeed in science, offering professional development based on data and dialogue, engaging teachers in standards-based curriculum revision and alignment, and recruiting the right fit of teacher). It is argued that best practice entails multiple levels of teaching and administrative praxis that together form a school-wide socio-ecological system conducive to higher performance.