Receptor tyrosine kinases of the Ryk and Ror families were initially classified as orphan receptors because their ligands were unknown. They are now known to contain functional extracellular Wnt-binding domains and are implicated in Wnt-signal transduction in multiple species. Although their signaling mechanisms still remain to be resolved in detail, both Ryk and Ror control important developmental processes in different tissues. However, whereas many other Wnt-signaling responses affect cell proliferation and differentiation, Ryk and Ror are mostly associated with controlling processes that rely on the polarized migration of cells. Here we discuss what is currently known about the involvement of this exciting class of receptors in development and disease.