An ideal denture base must have good physical and mechanical properties, biocompatibility, and esthetic properties. Various polymeric materials have been used to construct denture bases. Polymethyl methacrylate (PMMA) is the most used biomaterial for dentures fabrication due to its favorable properties, which include ease of processing and pigmenting, sufficient mechanical properties, economy, and low toxicity. This article aimed to comprehensively review the current knowledge about denture base materials (DBMs) types, properties, modifications, applications, and construction methods. We searched for articles about denture base materials in PubMed, Scopus, and Embase. Journals covering topics including dental materials, prosthodontics, and restorative dentistry were also combed through. Denture base material variations, types, qualities, applications, and fabrication research published in English were considered. Although PMMA has several benefits and gained popularity as a denture base material, it has certain limitations and cannot be classified as an ideal biomaterial for fabricating dental prostheses. Accordingly, several studies have been performed to enhance the physical and mechanical properties of PMMA by chemical modifications and mechanical reinforcement using fibers, nanofillers, and hybrid materials. This review aimed to update the current knowledge about DBMs’ types, properties, applications, and recent developments. There is a need for specific research to improve their biological properties due to patient and dental staff adverse reactions to possibly harmful substances produced during their manufacturing and use.