This review by Prashant K. Jain, Xiaohua Huang, Ivan H. El-Sayed, and Mostafa A. El-Sayed discusses the unique and tunable optical properties of noble metal nanoparticles, particularly gold (Au) and silver (Ag), due to their surface plasmon resonance (SPR). The authors highlight recent advancements in using these plasmonic properties for molecular-specific imaging, sensing, photo-diagnostics, and selective photothermal therapy. The SPR enhances the scattering and absorption of light from Au nanoparticles, making them useful as bright optical tags for biological imaging and detection. The SPR frequency is sensitive to the local medium dielectric constant, enabling its use in optical sensing of chemical and biological analytes. Additionally, plasmon coupling between nanoparticle pairs forms the basis for biodiagnostics and dynamic measurement of nanoscale distances in biological systems. The review also covers the historical and current applications of metal nanocrystals in photonics and biomedicine, emphasizing their tunable photophysical attributes, efficient addressability, and rapid advances in synthesis and fabrication.This review by Prashant K. Jain, Xiaohua Huang, Ivan H. El-Sayed, and Mostafa A. El-Sayed discusses the unique and tunable optical properties of noble metal nanoparticles, particularly gold (Au) and silver (Ag), due to their surface plasmon resonance (SPR). The authors highlight recent advancements in using these plasmonic properties for molecular-specific imaging, sensing, photo-diagnostics, and selective photothermal therapy. The SPR enhances the scattering and absorption of light from Au nanoparticles, making them useful as bright optical tags for biological imaging and detection. The SPR frequency is sensitive to the local medium dielectric constant, enabling its use in optical sensing of chemical and biological analytes. Additionally, plasmon coupling between nanoparticle pairs forms the basis for biodiagnostics and dynamic measurement of nanoscale distances in biological systems. The review also covers the historical and current applications of metal nanocrystals in photonics and biomedicine, emphasizing their tunable photophysical attributes, efficient addressability, and rapid advances in synthesis and fabrication.