In natural systems, structural macromolecules undergo prescribed recognition and assembly steps during synthesis and processing. These associations lead to more complex assemblies that exhibit useful multifunctional properties. Many of these processes are not well understood. Some aspects of these processes are presented using the fibrous protein polymer silk as an example. Issues such as polymer chain biosynthesis, chain interactions, processing into fibrils, and complex engineering into supra-assemblies are addressed and biochemical, spectroscopic and modeling studies are reviewed. Genetic level controls of chain composition, crystalline/amorphous domain distribution, chain aggregation, chain registry, silk I-silk II phase transitions, nematic liquid crystalline phase, loss of water, global molecular alignment, and solution spinning are some of the characteristics of this biological system that are addressed. Although some information is available at the molecular and macro-scale levels, a key issue is the paucity of information at the meso-scale level to fully understand the role of structural hierarchy in the silk fiber assembly process.