This practice guide offers research-based guidance for intensifying instruction in both reading and mathematics for students with significant learning difficulties, including students with disabilities in kindergarten through grade 12. To support educators in addressing the challenge of delivering effective intensive interventions, this guide discusses four considerations—integrating strategies that support cognitive processes (e.g., self-regulation and memory) with academic instruction and aligning this instruction with learner needs, differentiating instructional delivery by making it more explicit and systematic and by increasing opportunities for feedback, increasing instructional time, and reducing group size.