The immense power of Drosophila genetics has allowed invaluable insight into developmental biology. Despite these advances, a significant limitation has always been the lack of an efficient method for modifying select genetic loci. Now, on p. 4818, Jean-Paul Vincent and colleagues report high-efficiency homologous recombination in Drosophila with a novel gene-targeting vector. This can be achieved via a two-generation crossing scheme or via direct embryo injection. Importantly, both approaches yield few false-positives due to efficient negative selection, while readily detectable markers aid in the rapid identification of correctly targeted flies. The efficiency can be further increased by co-injecting the sequence-specific endonuclease CRISPR/Cas9. The investigators also report a series of vectors that can be used to insert different genetic elements into the targeted loci, such as mutated or tagged cDNAs and additional reporter genes. Their approach will enable genetic modification in a wide range of contexts, including in postmitotic cells. These tools will be a valuable resource for the Drosophila community.