The generation of morphological, such as left–right, asymmetry during development is an integral part of the establishment of a body plan. Until recently, the molecular basis of left–right asymmetry was a mystery, but studies indicate that Nodal and the Lefty proteins, transforming growth factor-β-related molecules, have a central role in generating asymmetric signals. Although the initial mechanism of symmetry breaking remains unknown, developmental biologists are beginning to analyse the pathway that leads to left–right asymmetry establishment and maintenance.