The ability of transcription factors to gain entrance to the nucleus is critical to their role in gene expression. Signal transducers and activators of transcription (STATs) are latent DNA binding factors activated by specific tyrosine phosphorylation. There are seven mammalian STAT genes encoding proteins that display constitutive nuclear localization and/or conditional nuclear localization. This review will focus on STAT1 and STAT2 that are activated in response to interferon and exhibit conditional nuclear localization. The dynamic redistribution of STAT1 and STAT2 between the cytoplasm and the nucleus is coordinate with their gain of ability to bind DNA.