Like many other viruses, adenovirus undergoes replication inside the host cell nucleus. The viral genome is packaged within a capsid that protects it from degradation and from detection by cellular defense systems in the cytoplasm, but the capsid needs to be disassembled before replication can occur. The viral capsid is far too large to pass through the nuclear pore, and how exactly the viral genome gets uncoated from the capsid and enters the nucleus is not clear. Now Greber and colleagues report that adenoviruses use a cellular motor, kinesin-1, to facilitate both processes. Using fluorescence and transmission electron microscopy analyses of adenovirus-infected cells, the authors observed that the disassembled viral capsids are associated with nucleoporins at the cytoplasm periphery. Because kinesin-1 is involved in anterograde transport of cellular and viral cargos, the authors tested kinesin-1 components and found that the light chains Klc1 and Klc2 and heavy chain Kif5C associate with adenoviral capsids and are required for their disassembly at the nuclear envelope and hence for viral infection. Kif5C was previously known to interact with the nuclear pore, resulting in activation of the ATP turnover by Kif5C in the presence of microtubules. Although the interaction of Kif5C with the nuclear pore complex was required for viral infection, it was not necessary for capsid association with the nuclear envelope. The specific interactions of viral capsid proteins with kinesin-1 and with nuclear pore components were mapped. The action of kinesin-1 on viral capsids docked to the nuclear pore resulted in disruption of the nuclear pore complex. The authors propose a model whereby kinesin-1 motor activity pulls apart the viral capsid; this separates the capsid from the genome and disrupts the nuclear pore complex, thereby facilitating entry of the adenoviral DNA into the nucleus. (Cell Host Microbe 10, 210–223, 2011)