Liposomes are widely used as drug delivery systems and several liposome-based nanomedicines have been approved for clinical use. Cell penetrating peptides (CPPs) have been decorated onto nanoparticulated vesicle such as liposomes to further improve the intracellular delivery efficiency. However, the poor selectivity of CPPs hindered their application, especially in the in vivo application. To resolve this issue, several strategies have been developed, including shielding and environment-triggered deshielding of CPPs as well as designing of environment-responsive CPPs and specific- targeting CPPs and last but not least, combination strategy. In this review, the abovementioned strategies were discussed.