Cell adhesion and migration are essential for embryonic development, tissue regeneration, but also for tumor development. The physical link between the extracellular matrix (ECM) and the actin cytoskeleton is mainly mediated by receptors of the integrin family. Through signals transduced upon integrin ligation to ECM proteins, this family of proteins plays key roles in regulating tumor growth and metastasis as well as tumor angiogenesis. During melanoma development, changes in integrin expression, intracellular control of integrin functions and signals perceived from integrin ligand binding impact upon the ability of tumor cells to interact with their environment and enable melanoma cells to convert from a sessile, stationary to a migratory and invasive phenotype. Antagonists of several integrins are now under evaluation in clinical trials to determine their potential as therapeutics for malignant melanoma and other kinds of cancer.