Although the lymphatic system has been initially described in the sixteenth century, basic research has been limited. Despite its importance for the maintenance of tissue fluid homeostasis and for the afferent immune response, research of the molecular mechanisms of lymphatic vessel formation and function has for a long time been hampered. One reason could be because of the difficulties of visibility due to the lack of lymphatic markers. But since the discovery of several molecules specifically expressed in lymphatic endothelial cells, a rediscovery of the lymphatic vasculature has taken place. New scientific insights has facilitated detailed analysis of the nature and organization of the lymphatic system in physiological and pathophysiological conditions, such as in chronic inflammation and metastatic cancer spread. Knowledge about the molecules that control lymphangiogenesis and tumor-associated lymphangiogenesis is now expanding, allowing better opportunities for the development of drugs interfering with the relevant signaling pathways. Advances in our understanding of the mechanisms have translated into a number of novel therapeutic studies.