Priorities and practices in teaching vary from culture to culture, yet there are commonalities in the brain and how people learn. It should be possible to identify a framework for teaching that can help teachers promote student learning across cultures. 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 teacher’s task is to successfully manage this complex interaction of cognitive challenges. The context-dependent nature of learning means that no single teaching method will always be optimal for all teachers, students, topics, and educational contexts.