Heterogeneity of tumors dictates an individual approach to anticancer treatment. Despite their variability, almost all cancer cells demonstrate enhanced uptake and utilization of glucose, a phenomenon known as the Warburg effect, whereas mitochondrial activity in tumor cells is suppressed. Considering the key role of mitochondria in cell death, it appears that resistance of most tumors towards treatment can be, at least in part, explained by mitochondrial silencing in cancer cells. This review is devoted to the role of mitochondria in cell death, and describes how targeting of mitochondria can make tumor cells more susceptible to anticancer treatment.