Novel gene technologies have allowed us to manipulate the genetic balance of candidate molecules in mice in a controllable manner. Homologous or site-speci®c recombination in embryonic stem cells allows us to study the consequences of de®ciencies, mutations, and conditional or tissue-speci®c expression of gene products in transgenic mice. These technological breakthroughs have signi®cantly advanced biomedical research and broadened our understanding of the pathophysiological role of candidate disease genes. In addition, gene transfer allows us to test the possible therapeutic use of gene products for gene therapy. A variety of assays have been miniaturized, allowing analysis of cardiovascular physiology in the mouse. With the advent of genome sequencing programmes, these gene technologies provide means of studying gene function in a conclusive manner. Furthermore, disease models can be generated which can be used as test models for (gene) therapy or for the discovery of novel genes using differential gene pro®ling techniques. The present review will focus on the molecular basis of how blood vessels form (angiogenesis and arteriogenesis) and how they become diseased. A selected number of molecules that have been studied in the authors' laboratory will be reviewed in more detail.