Cisplatin is one of the worldwide anticancer drugs and, despite its toxicity and frequent recurrence of resistance phenomena, it still remains the only therapeutic option for several tumors. Circumventing cisplatin resistance remains, therefore, a major goal for clinical therapy and represents a challenge for scientific research. Recent studies have brought to light the fundamental role of mitochondria in onset, progression, and metastasis of cancer, as well as its importance in the resistance to chemotherapy. The aim of this review is to give an overview of the current knowledge about the implication of mitochondria in cisplatin resistance and on the recent development in this research field. Recent studies have highlighted the role of mitochondrial DNA alterations in onset of resistance phenomena, being related both to redox balance alterations and to signal crosstalk with the nucleus, allowing a rewiring of cell metabolism. Moreover, an important role of the mitochondrial dynamics in the adaptation mechanism of cancer cells to challenging environment has been revealed. Giving bioenergetic plasticity to tumor cells, mitochondria allow cells to evade death pathways in stressful conditions, including chemotherapy. So far, even if the central role of mitochondria is recognized, little is known about the specific mechanisms implicated in the resistance. Nevertheless, mitochondria appear to be promising pharmacological targets for overcoming cisplatin resistance, but further studies are necessary.