In the past decade, several lines of evidence have highlighted the importance of the host cell cytoskeleton in various stages of retroviral infection. To complete their lifecycle, retroviruses must penetrate the outer barrier of the cell membrane, and viral cores containing the viral genome must traverse the cytoplasm to the nucleus and then viral gene products must make the journey back to the cell surface in order to release new progeny. The presence of a dense cytoskeletal network and organelles in the cytoplasm creates an environment that greatly impedes diffusion of macromolecules such as viruses. As such, retroviruses have evolved means to hijack actin as well as microtubule cytoskeletal networks that regulate macromolecular movement within the host cell. Developing studies are discovering several host and viral factors that play important roles in retroviral trafficking.