Tumor progression relies on angiogenesis from established normal vasculature to form new tumor blood vessels. Tumor endothelial cells (TECs) in the tumor blood vessels maintain tumor vessel formation through continual angiogenesis. TECs are heterogeneous with a diverse cellular origin. Moreover, the various factors and conditions in the tumor microenvironment elicit specific characteristics in TECs differentiating them from endothelial cells in normal vessels. TECs are the main focus of antiangiogenesis strategies, and their unique features make tumor blood vessels good anti-cancer therapeutic targets.