Integrins are heterodimeric transmembrane receptors that play an essential role in enabling cells to sense and bind to extracellular ligands. Activation and clustering of integrins leads to the formation of focal adhesions at the plasma membrane that subsequently initiate signalling pathways to control a broad range of functional endpoints including cell migration, proliferation and survival. The α4 and α9 integrins form a small sub-family of receptors that share some specific ligands and binding partners. Although relatively poorly studied compared with other integrin family members, emerging evidence suggests that despite restricted cell and tissue expression profiles, these integrins play a key role in the regulation of signalling pathways controlling cytoskeletal remodelling and migration in both adherent and non-adherent cell types. This review summarises the known shared and specific roles for α4 and α9 integrins and highlights the importance of these receptors in controlling cell migration within both homeostatic and disease settings.