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These days it's hard to imagine the world of functional genetics without the tools that RNAi has provided. The ability to knock down the function of a gene purely on the basis of


knowing its sequence has proved revolutionary, and has brought reverse-genetic approaches to systems where they were previously hard or impossible to apply. Not least among these newly


tractable systems are cell lines. The past few years have already seen exciting results from screens that have used RNAi on a large scale in mammalian and _Drosophila_ cells, shedding new


light on phenotypes that are as diverse as cell morphology, tumour-suppressor function and responses to infection. But the fact that large-scale RNAi screening in cells is now an established


approach doesn't mean that using the tools available is necessarily straightforward, nor that they cannot be improved on. On page 373 of this issue, Christophe Echeverri and Norbert


Perrimon provide a 'user's guide' to high-throughput RNAi screening, which takes the reader through the many choices that need to be made when planning such experiments. The


authors also delve into more complex issues that relate to optimization and quality control, and point out areas where future improvements are needed. High on the agenda for improvements in


RNAi screening are larger and more versatile libraries of silencing reagents. As reported in a recent issue of _Cell_ (see also the In Brief on page 331), the RNAi Consortium — a


public–private partnership — has developed a library that covers each of 22,000 mouse and human genes. Apart from its sheer size, this library can be used to silence genes in a wider range


of cell types than was previously possible. Clearly, we are only beginning to reap the benefits of the RNAi revolution. RIGHTS AND PERMISSIONS Reprints and permissions ABOUT THIS ARTICLE


CITE THIS ARTICLE From the editors. _Nat Rev Genet_ 7, 329 (2006). https://doi.org/10.1038/nrg1859 Download citation * Issue Date: May 2006 * DOI: https://doi.org/10.1038/nrg1859 SHARE THIS


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