Angiogenesis is the process of formation of new blood vessels from pre-existing vessels or endothelial cell progenitors. It plays an essential role in embryogenesis, inflammation, wound healing, tumor growth and metastasis. The tumor microenvironment contains excessive amounts of pro-angiogenic factors derived from neoplastic, stromal, and infiltrating immune cells. The imbalance of pro-angiogenic and anti-angiogenic factors promotes abnormal angiogenesis, creating numerous blood vessels with structural abnormalities and functional defects. These defective vessels often create an inflammatory environment within the tumor that promotes coagulation, thrombosis, and impairs blood supply, causing further complications to the cancer patient. The structural and functional abnormalities of the tumor vessels promote hematogenous metastasis, which is strongly associated with shorter patient survival. Furthermore, tumor blood vessels are poorly perfused, which impedes drug delivery to the tumor, thus reducing the efficacy of anti-cancer agents. Tumor angiogenesis is widely studied as an important target for suppressing tumor growth and metastasis. This review will briefly summarize the current findings related to regulation of angiogenesis by the tumor microenvironment, while highlighting potential targets for inhibiting this process.