One of the driving forces behind the characterisation of single gene diseases such as cystic fibrosis and complex disorders such as restenosis after angioplasty is the hope that novel therapies may emerge from a precise knowledge of the molecular pathophysiology. The development of a number of vector systems designed to deliver foreign genes to cells set the stage for the emergence of experimental gene transfer to investigate the function of individual genes, soon to be followed by gene therapy. In the early 1990s a number of review articles on the “gene therapy made easy” theme described the basic mechanisms by which studies with replication deficient adenoviruses and synthetic vectors could open up new possibilities for the treatment of vascular diseases.1 ,2 However, despite enormous enthusiasm, the application of gene transfer techniques in animal models has been problematic, and to date meaningful clinical benefit has not been realised in human studies. Moreover, fundamental difficulties in the basic biology of gene transfer techniques need to be addressed before real progress can be made in the application of this fashionable concept to the clinical arena.