Gamma radiation has been shown particularly useful for the functionalization of surfaces with stimuli-responsive polymers. This method involves the formation of active sites (free radicals) onto the polymeric backbone as a result of the high-energy radiation exposition. Thus a microenvironment suitable for the reaction among monomer and/or polymer and the active sites takes place leading to propagation which forms side chain grafts. The modification of polymers using high-energy irradiation can be performed by the following different methods: direct or simultaneous, pre-irradiation oxidative and pre-irradiation. The most frequent ones corresponds to the pre-irradiation oxidative method as well as the direct one. Radiation-grafting has many advantages over conventional methods because it does not require the use of catalyst nor additives to initiate the reaction, and usually no changes on the mechanical properties with respect to the pristine polymeric matrix are observed. This chapter is focused on the synthesis of smart polymers and coatings obtained by the use of gamma radiation. In addition the diverse applications of these materials in the biomedical area are also reported.