Over the last two decades the smart polymeric materials have involved the interest of the scientific community because they can be used in the design and formulation of dosage forms that respond, with a considerable variation of their properties, to changes in their environment. As result, these materials control the drug release into specific physiological compartments. Concerning on the environmental stimuli these include pH, temperature, light, chemicals, etc. The smart polymeric materials stimuli-responsive can be synthetics or naturals and have been used in the biotechnological, medicinal and engineering fields. The present chapter is aimed to focus the importance of this category of drug delivery systems and, in particular, it provides a summarizing overview of the range of smart polymeric materials and the drug delivery systems that exploit them.