Viral interaction with the microtubule (MT) cytoskeleton is critical to infection by many viruses. Most data regarding virus?MT interaction indicate key roles in the subcellular transport of virions/viral genomic material to sites of replication, assembly and egress. However, the MT cytoskeleton orchestrates diverse processes in addition to subcellular cargo transport, including regulation of signaling pathways, cell survival and mitosis, suggesting that viruses, expert manipulators of the host cell, may use the virus?MT interface to control multiple aspects of cell biology. Several lines of evidence support this idea, indicating that specific viral proteins can modify MT dynamics and/or structure and regulate processes such as apoptosis and innate immune signaling through MT-dependent mechanisms. Here, the authors review general aspects of virus?MT interactions, with emphasis on viral mechanisms that modify MT dynamics and functions to affect processes beyond virion transport. The emerging importance of discrete viral protein?MT interactions in pathogenic processes indicates that these interfaces may represent new targets for future therapeutics and vaccine development.