This chapter summarizes research and theory concerned with the effects of learner expertise (prior knowledge) on multimedia learning principles. The expertise reversal principle is that, in many situations, design principles that are effective for novice learners may not be effective or even hinder learning for more knowledgeable learners. The main theoretical issue associated with this principle concerns the integration in working memory of instructional information with knowledge structures held in long-term memory. The major instructional implication is the need to tailor instructional formats and procedures to changing levels of expertise. Essential research directions include identifying instructional procedures that are optimal for learners with different levels of expertise, investigating appropriate means for balancing the degree of instructional guidance provided to learners, and developing viable diagnostic instruments for the real-time evaluation of levels of learner expertise to be used in adaptive multimedia learning.