Signaling by the fibroblast growth factors (FGFs) and their receptors (FGFRs) has been implicated in a wide range of diseases including cancer and arthritis. The need to understand the mechanisms of these diseases, and the potential for the development of novel therapeutics, has driven the characterization of complexes of the FGFs, FGFRs, and the co-receptor heparin. These efforts have led to the proposal of two models, based on crystal structures, for the biological signaling complex: these models show considerable differences that are of great importance to the mechanism of signaling, but nevertheless share common themes. The merits of these models have been illuminated by a range of further crystal structures that have revealed the more relevant conformations of each model. The development of methods in ultracentrifugation and mass spectrometry has allowed the analysis of both complexes in solution, and has suggested that both architectures bind only one molecule of heparin. New methods for sequencing heparin and preparing heparin derivatives have allowed the affinity of FGFs for heparins to be determined. Finally, evidence has accumulated for complexes involving more than two FGFRs, and tantalizing hints have emerged of how both crystallographic models may contribute to a larger “signalosome”.