Protein-transduction technology is one of the most promising therapeutic tools for the control of intracellular events. A number of studies have demonstrated that minimal and efficient protein-transduction domains (PTDs) can act as a peptide vector to transfer bioactive cargo molecules from outside to inside the cell. PTD-mediated transduction has the ability to cross the blood-brain barrier, with transduction taking place in most tissues and cell types in vivo. Thus, recombinant proteins fused to or conjugated with PTDs have the potential to be harnessed as supplementary and/or intervention agents directly modulating cell signaling and/or metabolism, or to be applied to vaccine antigens/adjuvants that are efficiently delivered to the optimal site of action to enhance vaccine immunogenicity. This review introduces the mechanism of action, recent applications, and future perspectives of protein-transduction technology as an alternative therapeutic in the post-genome era.