Context: Unnecessary imaging and pathology procedures represent low-value care and can harm children and the health care system. Objective: To perform a systematic review of interventions designed to reduce unnecessary pediatric imaging and pathology testing. Data sources: We searched Medline, Embase, Cinahl, PubMed, Cochrane Library, and gray literature. Study selection: Studies we included were: reports of interventions to reduce unnecessary imaging and pathology testing in pediatric populations; from developed countries; written in the English language; and published between January 1, 1996, and April 29, 2017. Data extraction: Two researchers independently extracted data and assessed study quality using a Cochrane group risk of bias tool. Level of evidence was graded using the Oxford Centre for Evidence-Based Medicine grading system. Results: We found 64 articles including 44 before-after, 14 interrupted time series, and 1 randomized controlled trial. More effective interventions were (1) multifaceted, with 3 components (mean relative reduction = 45.0%; SD = 28.3%) as opposed to 2 components (32.0% [30.3%]); or 1 component (28.6%, [34.9%]); (2) targeted toward families and clinicians compared with clinicians only (61.9% [34.3%] vs 30.0% [32.0%], respectively); and (3) targeted toward imaging (41.8% [38.4%]) or pathology testing only (48.8% [20.9%]), compared with both simultaneously (21.6% [29.2%]). Limitations: The studies we included were limited to the English language. Conclusions: Promising interventions include audit and feedback, system-based changes, and education. Future researchers should move beyond before-after designs to rigorously evaluate interventions. A relatively novel approach will be to include both clinicians and the families they manage in such interventions.