Hydrogels are a versatile tool for a multitude of applications in biomedical research and clinical practice. Especially collagen and fibrin hydrogels are distinguished by their excellent biocompatibility, natural capacity for cell adhesion and low immunogenicity. In many ways, collagen and fibrin represent an ideal biomaterial, as they can serve as a scaffold for tissue regeneration and promote the migration of cells, as well as the ingrowth of tissues. On the other hand, pure collagen and fibrin materials are marked by poor mechanical properties and rapid degradation, which limits their use in practice. This paper will review methods of modification of natural collagen and fibrin materials to next-generation materials with enhanced stability. A special focus is placed on biomedical products from fibrin and collagen already on the market. In addition, recent research on the in vivo applications of collagen and fibrin-based materials will be showcased. © 2016 by De Gruyter.