Signal transduction pathways are often seen as cascades of kinases, whereas phosphatases are relinquished to the housekeeping function of resetting the individual elements to a resting state. However, critical biological processes such as cellular migration require a coordinated and constant remodeling of the actin cytoskeleton as well as a rapid turnover of the cell-substratum linkages that necessitate the concomitant action of antagonistic enzymes. Tyrosine phosphorylation was long known to be involved in adhesion and de-adhesion mediated via the integrin receptors. As the roles of tyrosine kinases such as focal adhesion kinase, c-Src, and Csk in this pathway are being extensively studied, increasing evidence is emerging about the importance of protein tyrosine phosphatases (PTP). In this review we discuss examples of PTPs that were recently shown to play a role in cell adhesion and migration and their mechanism of action.Key words: protein tyrosine phosphatases (PTP), migration, adhesion, FAK, p130Cas, Src.