The structural, dynamic and functional aspects of amino and carboxy-terminal regions in proteins of known structure have been analysed. Terminal regions are usually located on the surface of the protein, accessible to solvent, and are often flexible. There is a significant preference for terminal regions in single domain proteins, and within individual domains of larger proteins, to be in close proximity. This partially reflects the compact globular nature of proteins, but the preference for spatial proximity is stronger in native proteins than in randomly generated structures. In addition in multi-domain and multi-subunit proteins we find that the terminal regions are commonly involved in the interface between domains and subunits. In the 18 multi-domain structures analysed, 19 terminal regions provide a link between domains. Subunit links are also frequently observed. In contrast, the distribution of active site residues along the sequence, indicates that the terminal regions are less frequently involved in activity. These data suggest that in many globular proteins the terminal regions fulfil a structural role, stabilizing the tertiary or quaternary structure to provide a framework for the active site.