The development of new methods of nuclear transfer in mammals is creating many new opportunities in research, medicine and agriculture. The method of cloning is repeatable and has been established in many laboratories worldwide. However, the present procedure is inefficient with fewer than 4% of embryos becoming viable offspring. A considerable improvement in efficiency is required before wide scale use for livestock improvement. The opportunity to introduce precise genetic changes to livestock is available for the first time through the use of gene targeting procedures in cultured cells that are used as nuclear donors. This has potential application in the production of organs for transplantation to humans, studies of human genetic disease and basic research in to the control of gene expression and function.