At the beginning of 2016, first generation bioethanol still contributes to the majority of the 25 billion of gallons’ bioethanol produced worldwide, with the United States and Brazil producing approximately 85 % of the global production predominantly based on corn and sugarcane, respectively. However, concerns over the long-term sustainability of first generation bioethanol, such as the impacts on land use, water resource, the potential contamination of soils with the distillation residues, and the competition for food and feed production is frequently highlighted. Current fuel ethanol research and development strives to minimize these negative externalities. The fundamental role that process design plays during the development of cost-effective technologies is evaluated through the modification of the major pathways in first generation ethanol synthesis. In this context, the central role that better performing enzymes and microorganisms play in the intensity and integration of the process, such as the typical example of simultaneous saccharification and fermentation from starchy material in first generation facilities is acknowledged. Compensating ethanol production costs by the integrated valorization of energy and by-products for feed and green chemistry in a typical biorefinery concept are striking outputs of the first generation ethanol real scale experiment. Finally, rather than a mistake, first generation bioethanol should be considered as the first step that made it possible to gain the necessary experience for the successful implementation of the future greener generations biofuels from the field to the tank, starting with second generation lignocellulosic that is now coming on the market. In this context, integrated biorefineries are a promising way to diversify the usable feedstocks, leading to reduced facilities size and optimized supply-chains, to valorize more efficiently bagasse’s from sugarcane and corn stover or even to exploit the potential of microalgae to capture the carbon dioxide that is produced during the fermentation steps. Major stakeholders in bioenergy production are taking advantage of the large-scale successful development of first generation bioethanol, using the most promising processing schemes for next generation facilities, although the industry is still facing uncertainties with respect to its economic viability and longevity.