New insight has recently been obtained into the molecular mechanisms regulating lymphatic development and function during embryogenesis. VEGF-C and D ligands have been shown to stimulate lymphangiogenesis and their lymphatic-specific receptor VEGFR-3 is linked to the human congenital and hereditary lymphedema in humans. Above all, new focus on lymphatic endothelial cells gives opportunities for developing innovative therapies for lymphedema and cancer metastasis.