The RNAi facility is a world-class shared intramural resource whose mission is to conduct large-scale RNAi projects with collaborators throughout the NIH intramural program. To our knowledge, this is the only facility worldwide that allows investigators to receive genome-wide screens, hit confirmation, and analysis at no direct cost. This is ≈80% cheaper than contracting such an effort, and the facility?s workflow, throughput, and informatics surpass that of any other academic screening facility. The facility was commissioned by the Scientific Directors in late FY2008 and began infrastructure building, recruiting of staff, and pilot projects in FY2009. The facility became fully operational on schedule at the end of FY2010 and the first official projects were begun at the beginning of 2011. The facility assists with all stages of projects beginning with assay development, through validation and genome-wide siRNA screens, informatics/pathway analysis, and rigorous follow-up, including additional siRNAs for identified genes, real-time PCR confirmation, and confirmatory/mechanistic assays. Genome-wide siRNA screens for both human and mouse are conducted, and miRNA mimic and inhibitor libraries are routinely included in screens. The facility conducts ≈12 genome-wide screening projects per year.