Angiogenesis, the development of a microvasculature to a neoplastic, inflammatory, or infectious disease process, is a promising therapeutic target for disease therapy that has not been fully exploited. To further understand angiogenesis and its potential for therapy of dermatologic disorders, one must understand the many dualities of pathologic angiogenesis. These dualities are direct versus indirect angiogenesis inhibition, the differing origins of endothelial cells, which may arise either locally or through bone marrow stem cells, and regulation of vascular endothelial growth factor (VEGF) by hypoxia-dependent and/or independent pathways. The future development of therapy directed at pathologic angiogenesis is dependent upon an understanding of the factors that regulate angiogenesis. The presence of both direct and indirect inhibition of angiogenesis, the multiple sources of endothelial cells, and the regulation of VEGF by hypoxia-independent and/or-dependent pathways must taken into consideration if the promise of effective therapy of human disease is to be realized.