Novel gene technologies have allowed to manipulate the genetic balance of candidate molecules in mice in a controllable manner. Homologous or site-specific recombination in embryonic stem cells allows to study the consequences of deficiencies, mutations, conditional or tissue specific expression of gene products in transgenic mice. These technological breakthroughs have significantly advanced biomedical research and our understanding of the pathophysiological role of candidate disease genes. In addition, gene transfer allows to test the possible therapeutic use of gene products for gene therapy. With the advent of genome sequencing programs, these gene technologies provide means to study gene function in a conclusive manner. Furthermore, disease models can be generated which can be used as testmodels for (gene) therapy or for discovery of novel genes using differential gene profiling techniques. The present review will focus on the use of these technologies to study the molecular basis of how blood vessels form (angiogenesis) and how vessels can become affected by disorders. A selected number of molecules that have been studied in our laboratory will be reviewed in particular.