Stimuli responsive systems are an emerging area of research due to their ‘smart’ properties. They possess the ability to respond to various external stimuli that include pH, temperature, light, ionic concentration, magnetic field, electric field etc. The property of responsiveness is due to the presence of chemical and structural responsive functionalities that exhibit stimuli sensitiveness. In this chapter, some of the basic concepts of stimuli responsiveness are discussed with a section dedicated to protein-based stimuli responsive systems and their use in tissue engineering.