Despite extensive efforts regarding the potential anti-oxidant/anti-aging properties of different natural compounds over the last years, there is an emerging need to understand their precise biological functions. Oleuropein, the most abundant of the phenolic compounds in Olea europaea leaf extract, olive oil, and olives and therefore a major component of the traditional Mediterranean diet, extends the cellular lifespan and delays the appearance of the senescence morphology of human embryonic fibroblasts. Our results suggest that this is directly linked to its positive effects on proteasome function as well as to the decreased protein oxidation levels. However, a few aspects remain to be elucidated regarding oleuropein's biological function. For example, are there any other components of Olea europaea or even oleuropein's metabolites having proteasome activating properties? Does oleuropein regulate the transcription of proteasome subunits in addition to its properties to promote proteasome conformational alterations? Are there any additional properties of oleuropein that lead to the prolonged cellular lifespan and the maintenance of the young phenotype? Regardless of the outcome of future studies that will address these complementary questions, oleuropein is a natural anti-aging compound that offers the advantage that it can be easily taken up through normal diet.