Contrary to popular belief, pathogens have evolved not with the sole purpose of killing their hosts, but rather to multiply and spread efficiently under the pressure of natural selection. Our need to develop smart new therapeutic strategies to deal with bacterial and viral infections has stimulated serious efforts to understand the intimate relationship between host and pathogen. An unexpected spinoff from this work has been fresh insight into the molecular mechanisms underlying mammalian cell biology, particularly the organization and control of the actin and microtubule cytoskeletons. Bacteria and viruses have both exploited the unique properties of these dynamic, filamentous structures to facilitate their own life cycles. The report by Newsome et al.(1) on page 124 of this issue describes a mechanism by which vaccinia virus commandeers a host cell tyrosine kinase called Src to allow a smooth switch from microtubule-driven intracellular transport to actin-driven extracellular extrusion. Vaccinia virus is one of humanity’s best friends: It has lent its name to the most successful strategy yet for preventing infection and is responsible for eradicating smallpox from our planet. This virus is surrounded by an envelope and its DNA encodes close to 200 genes. After entering the cell, the viral core attaches to microtubules and moves to the perinuclear region of the host cell where the virus then replicates its DNA (2). A complex series of maturation steps leads to a viral core particle surrounded by two concentric membranes—this intracellular enveloped virus (IEV) then must make its way to the plasma membrane; for release. It has been estimated that because of its large size, this process would take more than 10 hours by diffusion. In fact, it takes the vaccinia virus less than a minute because the virus hitches a ride on kinesin, a host motor protein that normally transports cargo (protein complexes or vesicles) along microtubules to the cell periphery (see the figure, step 1). The viral A36R protein, which is the focus of the Newsome et al. report, plays a key role in this process. This protein is present