The extracellular matrix (ECM) was long thought to be merely a structural tissue support and/or a filter. However, recent studies have suggested that ECM proteins regulate many intracellular and extracellular events, including cell growth, cell adhesion, cell division, cell movement, and apoptosis. They do so through activation of several families of cell surface receptor, including the integrins and syndecans. The focus of this review is on two laminin isoforms expressed in the skin. Laminins are an important molecular component of the basement membranes in a variety of tissue types. They have a cruciform shape, and are composed of three chains-α, β, and γ. Keratinocytes of the skin secrete numerous laminin isoforms, including laminin-511 and laminin-332. The latter are known to affect the behaviour of keratinocytes through binding to membrane-penetrating receptors (outside-in signal transduction). Conversely, the expression, secretion and assembly of laminin-rich matrices is regulated by cell surface receptors through inside-out signal transduction. We will review how integrins regulate laminin matrix assembly and the signals elicited by laminins that support either migration or stable adhesion of keratinocytes. We will also discuss recent data indicating that laminins plays key regulatory roles in the development of skin appendages and contribute to the pathogenesis of skin cancer.