Angiopoietin-1 (Ang-1) is a secreted glycoprotein that plays a critical role in the development and maintenance of the vascular system. The angiopoietin (ANGPT)-TIE2/TEK signaling pathway is essential for blood and lymphatic vascular homeostasis. ANGPT1 is a potent TIE2 activator, whereas ANGPT2 functions as a context-dependent agonist/antagonist. Angiopoietin-1 can protect against pulmonary arterial hypertension, reduce the extent of fibrosis and remodeling in infarcted diabetic myocardium, and enhance tumor progression and metastasis.