Over the past two decades, the level of ethanol in wine has increased in most wine-producing regions, raising a number of issues related to consumer health, prevention policies, the effectiveness of the fermentation and wine sensorial quality. This review focuses on metabolic challenges and recent achievements in the development of Saccharomyces cerevisiae wine strains with reduced ethanol yield. Metabolic engineering approaches that have been successfully used to optimize endogenous pathways have been gradually replaced in recent years by evolutionary engineering strategies, which can generate strains with improved phenotypes using new circuits and can be put to immediate commercial use. The power of adaptive evolutionary strategies is expected to increase with the rapid development of whole-genome sequencing, which, combined with gene expression and metabolic flux analysis, enables the identification of the genetic basis of improved phenotypes and the transfer of such phenotypes between strains.