Most of the clinical gene therapy trials that have been initiated to date have employed ex vivo strategies in which cells are genetically modified outside the body and reimplanted. The ability to deliver genes accurately and efficiently to selected target cell populations in vivo would greatly expand the scope of gene therapy, but current vectors are not well suited to this task. Here we review recent attempts to develop retroviral vectors incorporating engineered envelope glycoproteins that are capable of delivering their genes in a highly specific manner to selected human target cells.