Gene therapy has the potential to treat devastating inherited diseases for which there is little hope of finding a conventional cure. In the late 1990s, our groups in Paris, London and Milan began treating children suffering from rare immune disorders (severe combined immunodeficiencies, or SCIDs). The successful treatment of the first patients was greeted with excitement when it was first reported in 2000 and 2002. Sadly, this euphoria turned to alarm at the end of 2002, when two of the ten children treated in France developed leukaemia-like conditions.