Transcription factors control numerous cellular processes, including proliferation, apoptosis, differentiation, and inflammation. Abnormal transcription factor activity has been implicated in a variety of diseases, especially cancer. The correct subcellular localization of transcription factors determines their activation status, implicating the nuclear transport receptors as key players in regulating transcription factor function. Dysregulation of the nuclear transport machinery has been described in numerous cancer types. This review summarizes how altered nuclear transport activity affects transcription factor localization and activity, and contributes to cancer development. Furthermore, the potential of targeting nuclear transporters for cancer therapy is discussed.