There is an increasing demand on the development of “smart” switchable interfaces since controlling surface topography and chemical functionality on a nanometer scale is crucial for numerous biomedical applications. Those surfaces, which are based on stimuli responsive polymers (SRPs), are able to modify their interactions with cells, biomolecules responding to different physical (e.g., temperature) or chemical (e.g., pH) stimuli. Such behavior may partially mimic complex dynamic properties of natural systems that are regulated by many biological stimuli. This paper reviews major studies and applications of SRPs as biointerfaces in a form of thin polymeric films (gels) and surface tethered polymers (brushes).