Angiogenesis is a critical step in the process of tumor metastasis. Many models have been used to study this process, but they have been artificial and do not reflect the actual process that takes place in the human being. Our laboratory has developed realistic models of angiogenesis based on orthotopic transplantation of human tumors in mice. In order to make angiogenesis visible in real time, our laboratory has developed mouse models in which the blood vessels are labeled with green fluorescent protein (GFP) such that they can be visualized by vascularizing tumors expressing red fluorescent protein (RFP). A particularly valuable model is a nude mouse in which the promoter from the stem-cell-marker protein, nestin, drives the expression of GFP. In such transgenic mice, the nascent blood vessels, in contrast to the mature blood vessels, express GFP. This model, in which human tumors expressing RFP are implanted, has been used to test drugs for their antitumor and antiangiogenetic activity. We have observed for the first time the high antiangiogenetic efficacy of cancer drugs such as gemcitabine and doxorubicin. These models should prove very valuable in the discovery of new antiangiogenesis drugs.