The increasing ability to manipulate the mouse genetically has created a model system that is both accessible and an accurate mirror of human development. A combination of analysis of existing spontaneous mouse mutations and creation of targeted mutations has identified at least z24 genes involved in the specification of mouse left-right asymmetry. These genes function in a carefully orchestrated manner first to create asymmetry at the node, then to signal it to the immediately surrounding cells via the node monocilia, and finally to amplify the initial asymmetry and propagate it to the developing organs. Defects at different steps in this pathway result in differences in the final phenotype. Human homologues exist for most of the mouse left-right determining genes. Notably, when human mutations in these genes have been identified in patients with defects of laterality determination, the human phenotype correlates very closely with the corresponding mouse phenotype.