The organization and mechanics of extracellular matrix (ECM) protein polymers determine tissue structure and function. Secreted ECM components are assembled into polymers via a cell-mediated process. The specific mechanisms that cells use for assembly are crucial for generating tissue-appropriate matrices. Fibronectin (FN) is a ubiquitous and abundant ECM protein that is assembled into a fibrillar matrix by a receptor-mediated process, and the FN matrix provides a foundation for incorporation of many other proteins into the ECM. In this Cell Science at a Glance article and the accompanying poster, we describe the domain organization of FN and the events that initiate and propagate a stable insoluble network of FN fibrils. We also discuss intracellular pathways that regulate FN assembly and the impact of changes in assembly on disease progression.