The nuclear membrane is a tight barrier for cytoplasmic proteins, but nuclear proteins have the intrinsic ability to overcome this barrier by an active signal-mediated process. Specific cytoplasmic carrier proteins have the responsibility to escort these proteins into the nucleus through the nuclear pore. The nuclear membrane is also a tight barrier for exogenous DNA delivered by synthetic vehicles, while many of the karyophilic viruses have a mechanism to actively deliver their genome through the nuclear pore. Virus DNA and RNA cannot move into the nucleus by themselves and require the viral structural proteins for efficient nuclear transport. In this article, we review the recent progress in understanding the mechanism of the nuclear transport of proteins and the virus genome, and discuss the possibility of developing synthetic gene-delivery systems based on these outcomes.