Abstract: Cell membrane serves as the natural barrier. Cell-penetrating peptides (CPPs) have been a powerful vehicle for the intracellular delivery of a large variety of cargoes cross the cell membrane. The efficiency of intracellular delivery of drugs, proteins, peptides and nucleic acid, as well as various nanoparticu-late pharmaceutical carriers (e.g., liposomes, polymeric micelles and inorganic nanoparticles) has been demon-strated both in vitro and in vivo. This review focuses on the CPPs-based strategy for intracellular delivery of small molecule drugs, proteins, peptides, nucleic acid and CPP-modified nanocarriers.