The effectiveness of different types of interventions to reduce low-value care has been insufficiently summarized to allow for translation to practice. This article systematically reviews the literature on the effectiveness of interventions to reduce low-value care and the quality of those studies. We found that multicomponent interventions addressing both patient and clinician roles in overuse have the greatest potential to reduce low-value care. Clinical decision support and performance feedback are promising strategies with a solid evidence base, and provider education yields changes by itself and when paired with other strategies. Further research is needed on the effectiveness of pay-for-performance, insurer restrictions, and risk-sharing contracts to reduce use of low-value care. While the literature reveals important evidence on strategies used to reduce low-value care, meaningful gaps persist. More experimentation, paired with rigorous evaluation and publication, is needed.