Fibrous proteins, such as silk, elastin and collagen are finding broad impact in biomaterial systems for a range of biomedical and industrial applications. Some of the key advantages of biosynthetic fibrous proteins compared to synthetic polymers include the tailorability of sequence, protein size, degradation pattern, and mechanical properties. Recombinant DNA production and precise control over genetic sequence of these proteins allows expansion and fine tuning of material properties to meet the needs for specific applications. We review current approaches in the design, cloning, and expression of fibrous proteins, with a focus on strategies utilized to meet the challenges of repetitive fibrous protein production. We discuss recent advances in understanding the fundamental basis of structure-function relationships and the designs that foster fibrous protein self-assembly towards predictable architectures and properties for a range of applications. We highlight the potential of functionalization through genetic engineering to design fibrous protein systems for biotechnological and biomedical applications. Biotechnol. Bioeng. 2016;113: 913-929. (c) 2015 Wiley Periodicals, Inc.