Psychological science has much to contribute to enhancing teaching and learning in the classroom. Teaching and learning are intricately linked to social and behavioral factors of human development, including cognition, motivation, social interaction, and communication. Psychological science can also provide key insights on effective instruction, classroom environments that promote learning, and appropriate use of assessment, including data, tests, and measurement, as well as research methods that inform practice. We present here the most important principles from psychology the “Top 20”—that would be of greatest use in the context of preK–12 classroom teaching and learning, as well as the implications of each as applied to classroom practice. Each principle is named and described, relevant supporting literature is provided, and its relevance for the classroom is discussed.