Since the discovery that baculoviruses can efficiently transduce mammalian cells, baculoviruses have been extensively studied as potential vectors for both in vitro and in vivo gene therapy. This chapter reviews the history of this research area, cells permissive to baculovirus transduction, factors influencing transduction and transgene expression, efforts to improve transduction, mechanisms of virus entry and intracellular trafficking, applications for in vivo and ex vivo gene therapy, as well as advantages, limitations, and safety issues concerning use of baculoviruses as gene therapy vectors. Recent progress and efforts directed toward overcoming existing bottlenecks are emphasized.