Fermentation performance of these biomass hydrolysates is limited by the lack of industrially suitable organisms to convert both glucose and xylose efficiently. To resolve this issue, several methods have been suggested, e.g., co‐cultivation of two or more species, engineering strains for enhanced substrate utilization, and use of sequential culture. Challenges of co‐culture include slower xylose fermentation due to varying affinities for oxygen, lower ethanol tolerance of xylose‐fermenters, and catabolite repression. Although successful engineering of microorganisms is demonstrated, there is limitation in understanding of the metabolic pathways regulations. Alternatively, sequential batch culture was suggested, but its productivity needs to be improved. Optimizing process conditions, e.g. process configuration, immobilization technique, cell type, enables improved yield and productivity. This paper reviews the approaches and conditions sought to improve glucose and xylose conversion from lignocellulosic hydrolysates to ethanol, with specific emphasis on microbial systems used to maximize biomass resource efficiency, ethanol yield, and productivity.