Transposable elements can be considered as natural, nonviral gene-delivery vehicles and are valuable and widely used tools for germ-line transgenesis and insertional mutagenesis in invertebrate systems such as flies and worms. Such tools were not available for genome manipulations in vertebrates until recently, when an active element was resurrected from transposon fossils found in fish genomes. This element, the Sleeping Beauty transposon, shows efficient transposition in cells of a wide range of vertebrates, including humans. Sleeping Beauty transposition is a cut-and-paste process, during which the element "jumps" from one DNA molecule to another. Transposon integration into chromosomes provides the basis for long-term, or possibly permanent, transgene expression in transgenic cells and organisms. Thus, the reconstruction of the Sleeping Beauty element generated considerable interest in developing efficient and safe vectors for vertebrate transgenesis as well as for human gene therapy. In this review we summarize our current knowledge of Sleeping Beauty biology and describe the strengths and current limitations of transposon technology for gene therapeutic applications.