Although the process of vascular development has been well documented, little is understood about lymphatic vasculature formation, despite its importance in normal and pathologic conditions. The dysfunction or abnormal growth of lymphatic vessels is associated with lymphedema and cancer metastasis. The recent discovery of lymphangiogenic growth factors vascular endothelial growth factor (VEGF)-C and VEGF-D and of their receptor, VEGFR-3, on lymphatic endothelial cells has started to provide an understanding of the molecular mechanisms of lymphangiogenesis. In addition, other genes that participate in the specification of lymphatic endothelial cells and the modulation of lymphatic vascular development have been identified. The capacity to induce or inhibit lymphangiogenesis by the manipulation of such molecules offers new opportunities to understand the function of the lymphatic system and to develop novel treatments for lymphatic disorders. This review describes the main players in lymphangiogenesis that have been identified so far and the attempts to shed some light on the mysteries surrounding this process.