According to the 2013 National Assessment of Academic Progress (NAEP) the majority of U.S. students are failing to reach developmentally appropriate levels of proficiency in several domains of study. Empirical research from educational and psychological perspectives on instructional strategies has great potential for identifying ways to improve student achievement in these areas. In particular, instructional strategies that utilize physical and virtual manipulatives are often proposed as effective means of improving educational outcomes. However, the benefits of manipulative-based instructional approaches are not uniformly observed across learners, treatments, outcomes, and settings. The present discussion reviews contemporary basic and applied research and makes research-based recommendations for classroom applications of instructional manipulatives. To accomplish these objectives we first provide an overview of the relevant theoretical explanations that support the assumed effectiveness of instructional strategies that use manipulatives. Second, we examine 6 central areas of instructional manipulatives research that have clear classroom applications. Lastly, we provide concrete examples of evidence-based ways in which manipulatives may be applied in classroom contexts.