The microbial surface components recognizing adhesive matrix molecules (MSCRAMMs) are a family of proteins that are defined by the presence of two adjacent IgG-like folded subdomains. These promote binding to ligands by mechanisms that involve major conformational changes exemplified by the binding to fibrinogen by the ‘dock-lock-latch’ mechanism or to collagen by the ‘collagen hug’. Clumping factors A and B are two such MSCRAMMs that have several important roles in the pathogenesis of Staphylococcus aureus infections. MSCRAMM architecture, ligand binding, and roles in infection and colonization are examined with a focus on recent developments with clumping factors. Shear stress mechanical forces trigger interactions between MSCRAMMs and their ligands.MSCRAMMs bound to ligands via the dock-lock-latch or collagen-hug mechanisms can only be separated by very strong forces.Clumping factor A has a crucial role in attachment to the endothelium during endovascular infections.Clumping factor B binding to loricrin is important in early abscess formation as well as in adhesion to corneocytes.MSCRAMMs also bind a plethora of ligands by mechanisms that do not involve dock-lock-latch.