The distinctive nuclear and cytoplasmic compartments of a eukaryote cell requires that metabolic processes which occur in the nucleus, such as gene transcription, are coordinated with related processes which occur in the cytoplasm. The steady state nuclear abundance of many transcription factors is the net outcome of a dynamic balance between nuclear import and nuclear export. Nuclear import and nuclear export mechanisms that govern the nucleocytoplasmic distribution of transcription factors are regulated at multiple levels, including post-translational modifications that alter the accessibility of cis-acting transport signals, binding and release from compartment-specific anchors, and the selective utilization of specific transport factors or specific nucleoporins. The net nuclear abundance of a transcription factor represents the integrated sum of multiple signal transduction pathways. Mechanisms that regulate nucleocytoplasmic transport of transcription factors may provide novel opportunities for drug development.