Hybrid materials comprising synthetic polymers and proteins or active enzymes combine the best of two worlds: The structural properties, the processibility and the moldability of man-made plastics or gels and the highly evolved functionality and responsiveness of nature?s polypeptides. In this chapter we review the body of literature on these smart hybrid materials and classify them according to their function. Biocatalytic plastics and polymers, stimuli-responsive hybrid hydrogels, self-assembled hydrogels with protein crosslinks, hybrid materials for selective binding of heavy metal ions, materials for tissue engineering, materials for controlled drug release, biodegradable materials, smart hydrogels with improved mechanical properties, and self-reporting materials are covered.