<p>Cerenkov radiation, first proposed by Pavel Cerenkov in the early 1900s, is the blue-weighted light produced by charged particles moving faster than the speed of light in a dielectric medium. Cerenkov radiation, which uses positron- and electron-emitting radionuclides commonly used in nuclear medicine applications, was investigated for medical imaging in the early 2000s, years after its initial discovery. It could reach clinical trials in optical imaging fields such as endoscopy, image-guided surgery, and tumor detection. In addition, it has been shown to have notable potential as an in situ light source to overcome the limitations of photodynamic therapy. However, as limited tissue penetration of the blue-weighted light of Cerenkov radiation remains a problem for both, nanoparticles have come to the fore to tackle this problem. This review aims to provide information on the application of Cerenkov radiation generated from radionuclides in imaging and therapy and the role of nanoparticles in these applications.</p>