The authors describe a research-based conceptual framework of how students learn that can guide the design, implementation, and troubleshooting of teaching practice. The framework consists of nine interacting cognitive challenges that teachers need to address to enhance student learning. These challenges include student mental mindset, metacognition and self-regulation, student fear and mistrust, prior knowledge, misconceptions, ineffective learning strategies, transfer of learning, constraints of selective attention, and the constraints of mental effort and working memory. The challenges are described with recommendations on how to address each one. What is effective for one situation may not be effective in others, and no single teaching method will always be optimal for all teachers, students, topics, and educational contexts. The teacher’s task is to manage this complex interaction successfully.