Smooth muscle cells (SMC) form the major cell type in the arterial blood vessels. In the undamaged vessel wall they remain in a contractile state characterized by the absence of cell division, a low metabolic activity and a high actin-myosin content. As a reaction to injury of the vessel wall they can, however, change their phenotype and start to proliferate and migrate through the vessel wall from the media towards the intima. Extracellular proteolysis is increased during the migration of SMCs and local lysis of the surrounding extracellular matrix is observed. The SMC produces several proteases during migration, especially plasminogen activators and metalloproteinases. Many growth factors and cytokines can modulate the production and activation of extracellular proteinases and their inhibitors in the activated vascular SMC. The production and regulation of the extracellular proteolytic enzymes by SMCs in relation to cell migration are discussed in this review.