Bacterial artificial chromosomes (BACs) have become a central tool in functional genomics. This is due to their average cloning capacity (around 150 Kb), which can accommodate most eukaryotic genes along with their full set of regulatory elements, and to their greater convenience in handling over other large cloning vectors like P1-based artificial chromosomes (PACs) and yeast artificial chromosomes (YACs). Two key advances for harnessing the full power of BACs have been the development of methods to modify them with precision and ease (see below), and the ability to use them for transgenesis in higher model organisms, like mouse and zebrafish (for review, see (1 )).