The use of high hydrostatic pressure (HHP) is an interesting approach to optimize the production of both first-and second-generation ethanol. It may be applied on Saccharomyces cerevisiae cells to enhance the fermentation pathway and on the lignocellulosic biomass to increase sugar release. HHP has a wide effect on many biological processes, such as growth, division and cellular viability. Actually, conformation, stability, polymerization and depolymerization of proteins are affected by HHP as well as lipid packaging. Moreover, transcriptional profile analysis indicates an activation of the general stress response. In yeast, HHP higher than 100 MPa leads to significant morphological and physiological alteration, and loss of cellular viability occurs over 200 MPa. A yield rate increase in ethanol production occurs at pressures of 10-50 MPa, but over 87 MPa alcoholic fermentation is interrupted.