Traditionally, a denture base is manufactured using a heat-cured acrylic resin. This type of resin was first used in dental labs in 1936, being a great step forward. Because of the many disadvantages as increased porosity, high water sorption, polymerization shrinkage, allergenic potential and citotoxicity due to the residual monomer, awkward flasking and packaging, and difficult processing, alternatives were continuously searched. Monomer-free and high-impact acrylics were developed, and gold plating of the denture base was experienced, in order to provide an alternative to allergic patients. Once polymers developed, new types of resins, such as polyamides (nylon), acetal, epoxy resins, styrene, polycarbonate, vinyl, urethane, polyether ether ketone (PEEK), became available on the dental market, accompanied by modern technologies, such as injection. CAD/CAM milled and 3D printed denture bases represent the present state of the art in this domain. Our chapter aims to present these alternative materials, which are safe to use in cases of allergic patients and guarantee a healthy oral environment and a high degree of comfort.