Improvements in the gene transfer vectors used in therapeutic trials have led to substantial clinical successes in patients with serious genetic conditions, such as immunodeficiency syndromes, blindness and some cancer types. Several barriers need to be overcome before this type of therapy becomes a widely accepted treatment for a broad group of medical diseases. However, recent progress in the field is finally realizing some of the promises made more than 20 years ago, providing optimism for additional successes in the near future.