Cisplatin is one of the most widely used and effective anticancer agents. It plays a major role in the chemotherapeutic treatment of a variety of cancers, including testicular, bladder, ovarian, head and neck, cervical, lung and colorectal cancer. The efficacy of cisplatin in cancer treatment, however, is limited due to either intrinsic or acquired cellular resistance in the tumors and severe side effects, especially in the kidney as well as ototoxicity. To overcome these limitations several strategies have been proposed, including the development of new improved platinating cytostatics. Our research focuses on the mechanism of action of newly synthesized platinum(IV) nitroxyl complexes, with special emphasis given to the effects on cellular resistance mechanisms such as decreased intracellular accumulation, increased drug detoxification, increased repair of cisplatin-induced DNA lesions and/or alterations of apoptotic cell death pathways. A detailed knowledge about the action of platinum(IV) nitroxyl complexes on tumor cells will help to clarify whether these complexes can be used for a more effective cancer treatment in the future.