During their lifetime T cells encounter many different environments and physical barriers. Depending on the context, T cells can adopt various motility strategies that facilitate their migration. Depicted here are some of the main motility modes employed by T cells. To enter tissues from the blood stream T cells undergo the multistep process of transendothelial migration (TEM) (A). This process includes both the crawling phase where T cells migrate over the endothelial monolayer (a 2D type of migration) in response to chemotactic cues and the diapedesis phase where T cells squeeze across the endothelial barrier. Within tissue parenchyma T cells may encounter a cell-dense environment (B), such as in secondary lymphoid organs, or an extracellular matrix (ECM)-dense environment (C), such as in the skin. ECM-dense environments may contain restrictive openings requiring substantial morphological changes to enable migration. In some tissues, T cells migrate along connected cell networks such as the fibroblastic reticular cells (FRCs) found in lymph nodes (D). T cells have also been reported to be able to switch to a bleb-based migration (E), where the formation of membrane blebs rather than a lamellipod or pseudopod directs migration at the leading edge.