A compelling vision for nanoparticles (NPs) in medicine involves their use to selectively diagnose, image, and destroy disease by throwing a noninvasive “switch.” is chapter explores the ability of laser light to be a switch that activates NPs accumulated in tissue to heat and destroy disease. NPs can be locally or systemically delivered such that they accumulate within the cellular and extracellular spaces of diseased tissue such as tumors. How NPs distribute throughout the body and tumors will be briey discussed, and comprehensive reviews will be noted. When present, the scattering of light by the NP can yield contrast for imaging, while light absorption by the NP can be used for therapeutic heating and photothermal imaging. While the advantages of using NPs for image contrast have been extensively reviewed by others (Qian 2008, Hu 2006, Zharov 2007), this chapter will focus on the ability and eects of NP laser heat generation at multiple scales. e potential advantages over traditional thermal therapies in terms of tumor specic destruction will be discussed. While various NPs are under investigation and some are in clinical trials, gold nanoparticles (GNP) are among the most mature for this technique due to the fact that they are among the strongest NP absorbers of laser light and are already being used clinically for photothermal treatment of cancer.