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Clickers, formerly known as instant response systems, have gradually become an integral part of the classroom. Though several reviews on research into clicker-integrated instruction have been published within this decade, the controversy over whether clickerintegrated instruction is effective to enhance students' learning gains has not been settled because the early reviews mainly focus on students' perceptions toward and acceptance of clicker-integrated instruction. Furthermore, so far there is no consistent and clear framework to explain why the use of clickers is effective or ineffective to facilitate academic learning outcomes. Based on the literature from the 1970s to the early 2010s, this review article identifies and summarizes the theoretical aspects accounting for possible relations between clicker-integrated instruction and academic learning outcomes. The theoretical aspects are subsequently evaluated and expanded in reference to primary studies. The results suggest that the superior effect of clicker-integrated instruction, compared to conventional lectures, stands on firm empirical ground. In addition, engaging students in explaining and justifying their answers to clicker questions is highly recommended because such an instructional strategy is associated with positive and strong effect sizes on academic learning outcomes.