Tissue engineering is a modern interdisciplinary field based on the principles of biology and engineering that has emerged as a therapeutic strategy aiming to replace lost or damaged tissues and organs in patients. The field combines knowledge and developments from the research areas of materials science, stem cells and developmental biology (growth and differentiation factors) with engineering. Current challenges in this area include the demand for multifunctional and mechanically robust three-dimensional (3-D) structures, the availability of the appropriate type of stem cells as well as the replication of the specific physiological environment during culture. Biomaterials constitute an essential component of tissue engineering. They are used to construct scaffolds that mimic the extracellular matrix in supporting tissue regeneration and ideally degrade at the same rate as that of the tissue growth. Both natural and synthetic biomaterials, polymers and ceramics, have been investigated in the fabrication of scaffolds, whereas lately hybrid organic-inorganic materials have attracted particular attention. The characteristics and importance of the multifunctionality and smart behavior of the biomaterials and scaffolds, in performing more than one action, during in vitro and in vivo tissue regeneration in specific applications are highlighted in this chapter.