Replacing fossil fuels by biomass-derived ethanol (also known as second-generation ethanol or bioethanol) can provide the dual benefits of renewability and mitigation of the effects of global warming caused by the overexploitation of petroleum-derived transportation fuels. However, the effective use of lignocellulosic biomass as a feedstock for the production of bioethanol is historically proven to be problematic and faces several technical challenges. A process configuration known as consolidated bioprocessing (CBP) has generated considerable research interests as the most cost-effective means of bioethanol production. However, insufficient production level of ethanol is the major roadblock, limiting their commercial importance. In this chapter, the research opportunities for developing thermoanaerobes for a high-temperature-based CBP and the associated technological challenges are discussed. The current industrial status of CBP is highlighted along with a detailed description of most promising candidate thermoanaerobes. Advanced technologies for improving the ethanol production level from these candidates are also discussed. A high-temperature-based biomass processing seems challenging; however, it could be the most rewarding approach for bioethanol production in the near future.