A fundamental impact of mitochondria on biological aging has been suggested decades ago. One prominent theory explains aging as the result of the age-related accumulation of random molecular damage of biomolecules resulting from the reaction of reactive oxygen species, the majority of which are generated in mitochondria. Although this concept appeared to be very attractive and strongly influenced aging research, in recent years more and more data accumulated which seem to contradict this theory. However, since these data are derived from reductionist approaches and do not integrate the various components and pathways which are affected as a result of a primary experimental intervention, they are prone to misinterpretation and have to be taken with some caution. Here, after a general introduction of mitochondrial function, we discuss the relevance of various pathways which are involved in keeping mitochondria functional over time. Moreover, we provide examples which emphasize the importance of a critical interpretation of experimental data and the necessity for a holistic analysis of the aging process. The success of such a systems biology approach is strongly dependent on the development of methods for data mining and an efficient analysis and modeling of the huge data sets that are raised.