Gene silencing through RNA interference (RNAi) has emerged as a powerful tool for understanding gene function. Over the past several years, high-throughput RNAi screens have illuminated a wide variety of biology ranging from genes that affect the activity of therapeutic agents to elucidating novel components of signaling pathways. NIH established a state-of-the-art RNAi screening facility that accepts proposals from any intramural researcher. This facility, administered by the NCATS Division of Pre-Clinical Innovation, assists with all stages of projects beginning with assay development through genome-wide siRNA screens, informatics/pathway analysis, and rigorous follow-up. Genome-wide siRNA screens for both human and mouse are available. Also routinely included in screens are miRNA mimic and inhibitor libraries.