Aging is the major risk factor for a constellation of multifactorial diseases, including insulin resistance, diabetes and cardiovascular complications. Dietary restriction has been shown to delay or prevent the manifestation of age-related health decline, extending lifespan in most species tested to date. Given the scarce willingness of human subjects to adhere to chronic dietary restriction exercises, there has been an interest in deciphering the molecular mechanisms triggering the adaptations to dietary restriction. In this context, Sirtuin 1 (SIRT1), a NAD+-dependent deacetylase enzyme, has been proposed to act as a key mediator of the adaptations to nutrient deprivation in eukaryotes, and SIRT1 activating compounds have been often referred to as 'dietary restriction mimetic' molecules. Here, we will discuss the convergences and divergences between the effects of dietary restriction and SIRT1 activation, based on the recent advances in the field. As of now, most evidences indicate that SIRT1 is required, but not sufficient to trigger dietary-restriction induced adaptations.