Laminins represent a growing family of disulfide-linked heterotrimers constituted by the association of three genetically different polypeptides, the alpha, beta, and gamma chains. Laminins are endowed with structural and biological functions. They play a direct critical role in the control of cellular behavior by providing cells with specific information through interactions with cell surface receptors. Because of their structural properties, they represent crucial building blocks for tissue assembly, architecture, and stability. The expression of laminin chain variants is spatio-temporally regulated, which suggests that laminin isoforms might have different functions responsible for the biological and morphological polymorphism of basement membranes. The different cells present in the skin express several laminin chains, which lead to the deposition of various laminin isoforms, whose mechanical and biological functions are likely to be adapted to the properties of the dermo-epidermal junction. Recently, defective laminin isoforms have been shown to be associated with several inborn and acquired diseases, illustrating a major structural function for laminins in skin integrity.