The production of D-ribose by fermentation has received much attention lately, possibly because of the use of this pentose to synthesize antiviral and anticancer drugs. This review briefly outlines the methods that have been used to synthesize D-ribose since it was identified in yeast RNA, and focuses in particular on the latest developments in D-ribose fermentation, which have led to D-ribose yields that exceed 90 g/l. Furthermore, the various transketolase-deficient D-ribose-producing mutants that are used, and the biochemical and genetic rationales applied to select them or to enhance their D-ribose productivities, are dealt with. Attention is also drawn to the unusual pleiotropic characteristics of the mutant strains, as well as to the industrial and academic applications of D-ribose.