The development of surfaces that have switchable properties, also known as smart surfaces, have been actively pursued in the past few years. The recent surge of interest in these switchable systems stems from the widespread number of applications to many areas in science and technology ranging from environmental cleanup to data storage, micro- and nanofluidic devices. Moreover, the ability to modulate biomolecule activity, protein immobilisation, and cell adhesion at the liquid-solid interface is important in a variety of biological and medical applications, including biofouling, chromatography, cell culture, regenerative medicine and tissue engineering. Different materials have been exploited to induce such changes in surface biological properties that are mostly based on self-assembled monolayers or polymer films. This critical review focuses on the recent progress in the preparation of these switchable surfaces, and highlights their applications in biological environments. The review is organized according to the external stimuli used to manipulate the properties of the substrate-chemical/biochemical, thermal, electric and optical stimuli. Current and future challenges in the field of smart biological surfaces are addressed (189 references).