Mouse ES cells have been used extensively in the generation of transgenic mice. These genetically modified mice are extremely useful, as they act as a model to study the functions of individual genes in a species close to humans. Transgenic mice are created by transferring a gene (for example a human cancer-related gene) into cultured ES cells. Alternatively, individual genes can be ‘knocked out’ by introducing a foreign gene—often a drug resistance protein—into a target gene. Unfortunately these gene manipulations are notoriously inefficient, and consequently the treated cells need to be grown in culture and selected for the correct gene change. The selected cells are then micro-injected into the inner cell mass of a normal embryo before implantation into the uterus of a foster mother mouse. The offspring have a copy of the introduced gene present in one of their paired chromosomes (i.e. they are heterozygous) and can be further bred to gain homozygous strains in which the new gene (or knocked out gene) has a copy in both matched chromosomes, so the effect will be apparent in every cell in the animal. Whether the gene is expressed in a particular tissue or cell type will depend on its genomic environment, something that can usually be directed at the ES cell level by careful molecular selection. There are now thousands of transgenic mice strains each with a specific gene alteration and they have greatly enhanced our understanding of many complex biological processes. When an error or the over expression of a particular gene is the major cause of a disease, transgenic animals can act as a model for developing new drugs or pharmaceutical interventions. Even when these genetic manipulations introduce changes that result in aborted foetuses, cell lines can be ‘rescued’ and grown in culture for useful research.