Purpose: To assess the effect of chemical disinfection procedures on the surface roughness of hard denture base materials. Materials and Methods: A systematic literature review was conducted using five electronic databases (Medline, Cochrane Library, OpenGrey, Lilac, and Google Scholar) along with hand searching of the bibliographies of all located articles. Results: The review yielded 193 articles. This number was reduced to 25 by using defined inclusion and exclusion criteria. Only one in vivo study was included; all others were in vitro evaluations. For every disinfecting agent, studies were found that reported surface alteration after chemical disinfection. The current literature suggests that changes in roughness might be more often associated with sodium perborate (three out of three studies with positive correlation) and less often with chlorhexidine digluconate and glutaraldehyde (two out of seven and one out of four studies with positive correlation, respectively). Because only single studies were found for glycine-type amphoteric surfactant solution, enzyme solution, ethanol, berberine hydrochloride, chlorine, reactive oxygen species, peracetic acid, cetylpyridinium chloride, and citric acid, no conclusions can be drawn about these disinfectants. Conclusions: Physical surface alteration is only one aspect when deciding on the use of chemical disinfection procedures. More research is needed to clarify whether these procedures can be recommended to patients.