Regenerative medicine, one of the most exciting and dynamic life science fields, is an emerging biomedical technology for assisting and accelerating the regeneration and repair of lost or damaged organs or body parts. Modern regenerative medicine is increasingly using three-dimensional structured scaffolds because they represent a wide range of morphological and geometric in vivo possibilities that can be tailored for each specific regenerative medicine application. This review focuses on polymeric scaffolds, a highly promising regenerative medicine strategy, summarizing some important issues related to various natural and synthetic scaffolding biomaterials, techniques on the design and fabrication of three-dimensional polymeric scaffolds to mimic the properties of the extracellular matrix, and clinical applications of polymeric scaffolds for tissue regeneration.