CD95 is best known for its capacity to induce apoptosis, but also activates multiple non-apoptotic signalling pathways. In particular, CD95 promotes migration and tissue invasion of apoptosis-resistant cell types, and this plays a central role in inflammation, neurobiology, and tumor biology. CD95 induces invasion by stimulating the expression of extracellular matrix (ECM)-degrading proteases, and by stimulating the formation of actin-driven cell protrusions through Rac and the cofilin pathway. In this review we discuss how CD95-initiated signalling pathways may cooperate to facilitate cell migration and tissue invasion.