Saccharomyces cerevisiae and Kluyveromyces lactis are considered to be the prototypes of two distinct metabolic models of facultatively-aerobic yeasts: Crabtree-positive/fermentative and Crabtree-negative/respiratory, respectively. Our group had previously proposed that one of the molecular keys supporting this difference lies in the mechanisms involved in the reoxidation of the NADPH produced as a consequence of the activity of the pentose phosphate pathway. It has been demonstrated that a significant part of this reoxidation is carried out in K. lactis by mitochondrial external alternative dehydrogenases which use NADPH, the enzymes of S. cerevisiae being NADH-specific. Moreover, the NADPH-dependent pathways of response to oxidative stress appear as a feasible alternative that might co-exist with direct mitochondrial reoxidation.