Saccharomyces cerevisiae, budding yeast, and Schizosaccharomyces pombe, fission yeast, are the most common and important experimental eukaryotic microorganisms in biochemical research. Although the two yeasts exhibit similar cellular and biochemical activities, some of their metabolic differences have been documented. D-Glucose is utilized anaerobically by fermentative metabolism while it undergoes respirative or respirofermentative metabolism aerobically depending on growth conditions. Both Saccharomyces cerevisiae and Schizosaccharomyces pombe catabolize D-glucose for growth and for energy metabolism via ubiquitous glycolysis, pentose phosphate pathway and tricarboxylate cycle. Many of the key enzymes for these pathways have been purified and characterized from S. cerevisiae. Properties and functions of these enzymes will be examined. The budding yeast which displays an inducible glyoxylate cycle is capable of growing in acetate culture, whereas the fission yeast is unable to grow in a medium with acetate as the sole carbon source because of an absence of the glyoxylate cycle. Glycerol utilization is initiated by phosphorylation in Saccharomyces cerevisiae while it is initiated by oxidation in Schizosaccharomyces pombe. Evidence is presented to show that D-glucose can be metabolized via an alternative D-gluconate pathway in Schizosaccharomyces pombe. The significance of these metabolic differences in the D-glucose utilization by the budding yeast versus the fission yeast will be discussed.