The function of many key proteins and transcription factors involved in cell growth can be regulated by their cellular localization. Such proteins include the tumor suppressor p53 and the nuclear factor κB. Although the idea of trapping such proteins in either the nucleus or cytoplasm has been introduced as a potential therapeutic target, only two nuclear transport inhibitors have been reported. Here, we explore the roles of small-molecule inhibitors that cause target proteins to sequester in either the nucleus or cytoplasm. Methods of artificially targeting proteins to the nucleus or cytoplasm using peptide aptamer technology are also discussed.