The availability of the whole genome sequence of many model organisms, combined with well-established chemical mutagenesis methods and cost-effective high-throughput DNA genotyping, allows mutations to be identified for virtually any gene. Recently dubbed TILLING (for targeting induced local lesions in genomes), this general method is gaining popularity. In this article, I discuss some of the TILLING methods that are available, the successes that have been reported for several organisms and the future outlook for such methods.