A key feature of any living system is the ability to sense and react to the environmental stimuli. The biochemical characterization of the underlying biological sensors combined with advances in polymer chemistry has enabled the development of stimulus-sensitive biohybrid materials that translate most diverse chemical and biological input into a precise change in material properties. In this review article, we first describe synthesis strategies of how biological and chemical polymers can functionally be interconnected. We then provide a comprehensive overview of how the different properties of biological sensor molecules such as competitive target binding and allosteric modulation can be harnessed to develop responsive materials with applications in tissue engineering and drug delivery. Stimulus-sensing biohybrid materials have attracted significant interest as smart materials with applications especially in the biomedical field. Such materials harnessing unique properties of chemical and biological polymers are engineered to translate molecular stimuli into precisely defined mechanical material properties. This article gives an overview of how biological polymers can be used to control material properties and on their applications. © 2013 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.