This review discusses the classical nuclear localization signal (cNLS), its function in nuclear import, and its interaction with importin α. The classical nuclear import pathway is the best understood system for transporting macromolecules between the cytoplasm and the nucleus. In this pathway, a protein containing a cNLS is imported by a heterodimeric import receptor consisting of importin β, which mediates interactions with the nuclear pore complex, and importin α, which directly binds the cNLS. Recent studies have advanced our understanding of this pathway, and a bioinformatics approach has been used to analyze the likely prevalence of this system in vivo. In eukaryotic cells, the nuclear envelope separates the genetic material and transcriptional machinery from the translational machinery and metabolic systems of the cytoplasm. This segregation allows for the precise regulation of cellular processes such as gene expression, signal transduction, and cell cycle progression through selective regulation of bidirectional transport between the nucleus and the cytoplasm. Nuclear transport systems were first proposed when a nuclear targeting signal in the simian virus 40 (SV40) large T antigen was characterized over 20 years ago. Since then, several pathways for nucleocytoplasmic transport have been described, of which the classical nuclear import pathway is the best characterized. The classical nuclear import cycle involves the recognition of the cNLS by importin α, which links it to importin β. Importin β then mediates interaction of the trimeric complex with the nuclear pore as it translocates into the nucleus. Once the import complex reaches the nucleus, it is dissociated by RanGTP. Binding of RanGTP to importin β causes a conformational change that results in the release of the importin α-cargo complex. The autoinhibitory region on the importin β-binding (IBB) domain of importin α, along with nucleoporin Nup2 and the export receptor for importin α, Cse1/RanGTP, work together to deliver the cargo into the nucleus. Finally, Cse1/RanGTP recycles importin α back to the cytoplasm in preparation for another round of import. The classical NLS is often thought of as the prototypical NLS. It was the first NLS to be characterized, and as such, many examples of proteins using the classical import pathway have been characterized. However, no studies have established empirically the proportion of cargos imported via this mechanism. It is possible that other pathways account for a large amount of nuclear traffic. To address this issue, the prevalence of classical NLSs was estimated using the well-annotated S. cerevisiae genome and known consensus sequences for monopartite and bipartite cNLSs. The results indicate that classical nuclear import may indeed be as important as the name implies, as about 45% of the proteins in the cellThis review discusses the classical nuclear localization signal (cNLS), its function in nuclear import, and its interaction with importin α. The classical nuclear import pathway is the best understood system for transporting macromolecules between the cytoplasm and the nucleus. In this pathway, a protein containing a cNLS is imported by a heterodimeric import receptor consisting of importin β, which mediates interactions with the nuclear pore complex, and importin α, which directly binds the cNLS. Recent studies have advanced our understanding of this pathway, and a bioinformatics approach has been used to analyze the likely prevalence of this system in vivo. In eukaryotic cells, the nuclear envelope separates the genetic material and transcriptional machinery from the translational machinery and metabolic systems of the cytoplasm. This segregation allows for the precise regulation of cellular processes such as gene expression, signal transduction, and cell cycle progression through selective regulation of bidirectional transport between the nucleus and the cytoplasm. Nuclear transport systems were first proposed when a nuclear targeting signal in the simian virus 40 (SV40) large T antigen was characterized over 20 years ago. Since then, several pathways for nucleocytoplasmic transport have been described, of which the classical nuclear import pathway is the best characterized. The classical nuclear import cycle involves the recognition of the cNLS by importin α, which links it to importin β. Importin β then mediates interaction of the trimeric complex with the nuclear pore as it translocates into the nucleus. Once the import complex reaches the nucleus, it is dissociated by RanGTP. Binding of RanGTP to importin β causes a conformational change that results in the release of the importin α-cargo complex. The autoinhibitory region on the importin β-binding (IBB) domain of importin α, along with nucleoporin Nup2 and the export receptor for importin α, Cse1/RanGTP, work together to deliver the cargo into the nucleus. Finally, Cse1/RanGTP recycles importin α back to the cytoplasm in preparation for another round of import. The classical NLS is often thought of as the prototypical NLS. It was the first NLS to be characterized, and as such, many examples of proteins using the classical import pathway have been characterized. However, no studies have established empirically the proportion of cargos imported via this mechanism. It is possible that other pathways account for a large amount of nuclear traffic. To address this issue, the prevalence of classical NLSs was estimated using the well-annotated S. cerevisiae genome and known consensus sequences for monopartite and bipartite cNLSs. The results indicate that classical nuclear import may indeed be as important as the name implies, as about 45% of the proteins in the cell