Various types of nanoparticles efficiently heat in radiofrequency fields, which can potentially be used to produce cancer cell cytotoxicity within minutes. Multifunctional and targeted nanoparticles have demonstrated effective cancer control in vivo without significant toxicity associated with radiofrequency field exposure. Importantly, animals treated systemically with targeted nanoparticles smaller than 50 nm demonstrate tumor necrosis after radiofrequency field exposure without acute or chronic toxicity to normal tissues. Likewise, the future holds great promise for multifunctional imaging as well as multimodality therapy with chemotherapeutic molecules and ionizing radiation sensitizing agents attached to nanoparticle constructs. However, the appropriate balance of safety and efficacy for diagnosis, therapy, and therapeutic monitoring with these nanoparticles remains to be fully elucidated.