Information can be transferred between the nucleus and the cytoplasm by translocating macromolecules across the nuclear envelope. Communication of extracellular or intracellular changes to the nucleus frequently leads to a transcriptional response that allows cells to survive in a continuously changing environment. Eukaryotic cells have evolved ways to regulate this movement of macromolecules between the cytoplasm and the nucleus such that the transfer of information occurs only under conditions in which a transcriptional response is required. This review focuses on the ways in which cells regulate movement of proteins across the nuclear envelope and the significance of this regulation for controlling diverse biological processes.