Integrin-linked focal adhesion complexes provide the main sites of cell adhesion to extracellular matrix and associate with the actin cytoskeleton to control cell movement. Dynamic regulation of focal adhesions and reorganization of the associated actin cytoskeleton are crucial determinants of cell migration. There are important roles for tyrosine kinases, extracellular signal-regulated protein kinase/mitogen-activated protein kinase signalling, and intracellular and extracellular proteases during actin and adhesion modulation. Dysregulation of these is associated with tumour cell invasion. In this article, we discuss established roles for these signalling pathways, as well as the functional interplay between them in controlling the migratory phenotype.