When hobbyist Chobei Zenya wrote The Breeding of Curious Varieties of the Mouse in 1787, he probably never imagined the impact that mouse breeding would eventually have on biomedical and genetic research. During the past two centuries, the "fancy mice" once prized by breeders have evolved into the multitude of inbred strains now used to study complex genetic traits and to model human diseases. In the past 40 years, mouse biology has exploded, as scientists added to the heap with transgenics, knockouts, and cloned mice. This issue's Hot Papers chronicle the next milestone in the life of Mus musculus, its genome.