As little as five years ago, the idea that it would be possible to generate an ovine model of cystic fibrosis (CF) was frequently met with humour and disbelief. Fortunately for those of us attempting to produce a large animal model of this debilitating disease, the generation of cloned sheep (1,2) changed all of that. The case must now be made for the production of an ovine model for CF. The justification may be applied to large animal models of many other human genetic diseases. Recent data showing that the cloning technology is applicable to other species, such as the cow (3), provide further support for the feasibility of this approach.