In this article, we will review: 1) an introduction describing the links between obesity and metabolic syndrome with lymphatic dysfunction and lymphedema 2) a brief synopsis of the lymphatic vasculature to introduce the lymphatic collecting vessels; 3) our understanding of the necessity of the lymphatic pump in physiology; 4) ionic and molecular mechanisms underlying lymphatic contractions; 5) the role of eNOS in lymphatic collecting vessel function and dysfunction; 6) contractile dysfunction in metabolic disease; 7) potential pharmacological targets. Here, NOS3 is linked to metabolic disease.