There have been major advances in our understanding of the molecular biology and pathophysiology of human disease over the past decade. This expanding knowledge of the basic mechanisms of human disease coupled with the development of efficient methods of transferring genes to mammalian cells has stimulated considerable interest in treating diseases with gene therapy. Clinical trials have demonstrated that human gene transfer is possible, that several strategies exist for successfully introducing exogenous genes to human cells, that a variety of transgenes can evoke biologic responses important to human diseases, and that gene transfer can provide valuable insights into the pathophysiology of human disorders. Initial clinical trials have yielded encouraging results and adverse reactions have been uncommon. Despite the advances in human gene transfer, significant obstacles need to be overcome before it becomes a firmly established therapeutic option for human illness. The potential benefits of utilizing human gene therapy in the treatment of hereditary and acquired disease have generated interest in further advancing this remarkable technology.