 Advances in the extraction, purification, and characterization of keratin proteins from hair and wool fibers over the past century have led to the development of a keratin-based biomaterials platform. Like many naturally derived biomolecules, keratins have intrinsic biological activity and biocompatibility. In addition, extracted keratins are capable of forming self-assembled structures that regulate cellular recognition and behavior. These qualities have led to the development of keratin biomaterials with applications in wound healing, drug delivery, tissue engineering, trauma, and medical devices. This review discusses the history of keratin research and the advancement of keratin biomaterials for biomedical applications.