ABSTRACT Basement membranes (BMs) underlie or surround most tissues. They are formed of secreted proteins that associate with cell surfaces and are the most ancient animal extracellular matrix. Laminin and collagen IV are core components that polymerize into self-associating networks, providing BMs with an organizing scaffold and tensile strength. In humans, BMs also contain over 150 other secreted proteins, such as structural matrix components, enzymes and growth factors, as well as over 50 cell–membrane adhesion and signalling receptors. From this toolbox, BMs are tailored for tissue-specific functions, including filtration, shaping organs, connecting tissues and harbouring signals that guide cell migration and differentiation. Highlighting their importance to human health, defects in genes encoding BM proteins are associated with over 100 disease phenotypes. Advancing our understanding of BM regulation, function and dysregulation will reveal new approaches to prevent many human disorders and preserve tissue health. Here, we review our current understanding of BM composition, formation and function, and outline how BMs change with ageing and disease.