The nuclear pore complex can be considered to be the stationary phase of bidirectional traffic between the nucleus and the cytoplasm. The mobile phase consists of karyopherins, transport substrates, and the small GTPase Ran and its modulators. Recently, the family of karyopherins was expanded with the recognition of numerous open reading frames with limited homology to karyopherin beta 1. In several cases, the specific substrates transported by the new karyopherins have been identified, allowing the characterization of new pathways into and out of the nucleus. However, the mechanisms of transport, particularly the role of Ran, remain poorly understood.