A compelling vision in nanomedicine is the use of self directed nanoparticles that can accumulate in areas of disease to perform designed functions, such as molecular delivery or destruction, endosomal release of genes or siRNA, and selective cell or tumor destruction with nano to macroscale spatiotemporal control and precision. These functions are increasingly achieved by gold nanoparticles (GNPs, such as sphere, shell or rod) that can be activated with a laser “switch”. A defining aspect of this “switch” is GNP absorption of laser light and the ensuing heat generation and temperature change that can be confined or propagated through multiple scales from the nanoparticle surface up through bulk biological cells and tissues. In this critical review, we discuss the fundamental mechanisms of laser GNP heat generation, the measurement and modelling of the ensuing thermal response, and a number of the evolving biological applications dependent on this new technology (181 references).