Angiopoietin-2 (Ang2) is a member of the Ang family, which plays an important role in angiogenesis during the development and growth of human cancers. Ang2's role in angiogenesis generally is considered as an antagonist for Ang1, inhibiting Ang1-promoted Tie2 signaling, which is critical for blood vessel maturation and stabilization. Ang2 modulates angiogenesis in a cooperative manner with another important angiogenic factor, vascular endothelial growth factor A. Genetic studies have revealed that Ang2 also is critical in lymphangiogenesis during development. However, new evidence suggests more complicated roles for Ang2 in angiogenesis in physiologic processes and invasive phenotypes of cancer cells during progression of human cancers. This article discusses recent studies of Ang2 in angiogenesis and the implication of Ang2 as a therapeutic target as well as a potential inhibitor for antiangiogenesis treatment for cancer patients.