Tissue conditioners (TCs) are short-term soft liners, formed in situ from a mixture of a polymer powder and a liquid plasticizer. This article reviews the recent advances in the composition, functions, clinical use, gelation process, and physical properties of TCs and their effects on denture bases and oral mucosa. TCs are used to improve the fit and function of an ill-fitting denture. They can also be used to treat abused mucosal tissues underlying ill-fitting acrylic dentures as temporary expedients. TCs are recommended as provisional liners to maintain the fit of removable dentures and to prevent mechanical irritation from the denture. TCs may also be used to rehabilitate cancer patients. The polymer powder, used in the formulation of TCs generally consists of polyethyl methacrylate (PEMA) and the liquid plasticizer is ester-based in ethyl alcohol solution without an acrylic monomer. The plasticizers are low molecular weight aromatic esters. Mixing of the powder and liquid results in polymer chain entanglement and the formation of a coherent gel characterized by viscoelastic behavior appropriate to its intended clinical use. The loss of surface integrity and surface roughness of TCs are regarded as the main problems in the denture bearing oral mucosa conditions resulting in inflammation of oral mucosa of the denture-bearing area -denture stomatitis. TCs provide an even distribution of masticatory force, accurately modeling itself to the changes which occur during the healing of lesion of substrate and can act therapeutically by incorporating antifungal or antibacterial agents.