Active transport between the nucleus and cytoplasm involves primarily three classes of macromolecules: substrates, adaptors, and receptors. Some transport substrates bind directly to an import or an export receptor while others require one or more adaptors to mediate formation of a receptor-substrate complex. Once assembled, these transport complexes are transferred in one direction across the nuclear envelope through aqueous channels that are part of the nuclear pore complexes (NPCs). Dissociation of the transport complex must then take place, and both adaptors and receptors must be recycled through the NPC to allow another round of transport to occur. Directionality of either import or export therefore depends on association between a substrate and its receptor on one side of the nuclear envelope and dissociation on the other. The Ran GTPase is critical in generating this asymmetry. Regulation of nucleocytoplasmic transport generally involves specific inhibition of the formation of a transport complex; however, more global forms of regulation also occur.