This chapter examines the ways in which the assembly processes observed during in vitro fibrillogenesis are related to fibril assembly in vivo, and to see if some illuminating common ground can be found between the two systems. In vitro fibrillogenesis experiments are normally conducted with purified solutions of collagen molecules, extracted from tissues containing the collagen type of interest. Fibroblasts are amongst the components not normally present during in vitro fibrillogenesis studies. The assembly of collagen fibers in vivo has to be considered in a quite different light than in the in vitro situation. The situation in vivo may differ from that in vitro in that not only are the telopeptides likely to be completely intact, but that the molecule may possess the N-terminal extension propeptide right up to the time of incorporation of the molecule into the fibril. The nonhelical telopeptides of type one collagen contain the sites of residues involved in the aldehyde-mediated covalent cross-linking of the fibrils.