Extravasation, the process by which tumor cells leave the circulation by transmigrating through the endothelium that lines blood vessel walls, is an essential step for metastasis towards distant organs. As such, reducing extravasation of cancer cells is a potential approach to inhibit metastasis. Rho GTPases are small signalling G-proteins that are central regulators of cytoskeleton dynamics, and thereby mediate several steps of the metastatic cascade, including invasion, migration, and extravasation of cancer cells. Additionally, RhoGTPase signalling networks regulate cancer cell-endothelial cell interactions and are involved in the disruption of the endothelial barrier function, allowing cancer cells to extravasate the underlying tissue. Thus, targeting Rho GTPase signalling networks may be an effective approach to inhibit extravasation and metastasis. In this review, the roles and regulation of Rho GTPase signalling networks in cancer cell extravasation will be discussed, both from a cancer cell and endothelial cell point of view.