Multifunctional scaffolds based on smart materials have been applied in different tissue engineering fields. The most frequently studied areas in the literature include the use of multifunctional scaffolds in bone, cartilage and muscle formation, in cardiovascular and endothelium tissue engineering, in the growth of skin and in neural regeneration. Other applications include their use in dental, corneal and retina tissue engineering as well as in wound healing. This chapter will focus on the most extensively studied tissues of which the understanding and knowledge have matured the most. Although multifunctional materials and stimuli-sensitive nanoparticulate drug delivery systems have also shown great therapeutic potential for various cardiovascular and infectious diseases and cancer,5 this application will not be discussed here. In the following, the sections are divided based on the respective tissue of interest, for which the material characteristics and the multifunctionality of materials and scaffolds are discussed. The potential clinical applications of the multifunctional scaffolds are also considered.