Haploid genetics holds great promise for understanding genome evolution and function. Much of the work on haploid genetics has previously been limited to microbes, but possibilities now extend to animal species, including mammals. Whereas haploid animals were described decades ago, only very recent advances in culture techniques have facilitated haploid embryonic stem cell derivation in mammals. This article examines the potential use of haploid cells and puts haploid animal cells into a historical and biological context. Application of haploid cells in genetic screening holds promise for advancing the genetic exploration of mammalian genomes.