The extracellular matrix consists of multifunctional molecules, which are composed of a large numbers of different domains. Clearly these domains and even the entire molecules do not function independently as isolated species, but interact with each other in large networks. In many cases specific regions of the networks may be considered as molecular machines in which the different molecules are arranged in highly defined spatial structures and act in a dynamic, concerted fashion. At present most structural information is limited to single molecules, and dynamics have been measured mainly for pairs of interacting partners in solution. Work needs to be extended to large integrated systems and the functions of molecular machines need to be explored. Electron tomography, fluorescence resonance energy transfer, and other biophysical techniques are very promising.