<p>Bioluminescence, the light generated through biochemical reactions involving luciferases in living organisms, has been the focus of extensive research due to its diverse applications. It is especially noteworthy as an internal light source for theranostic applications because of its safety and efficiency, which helps to overcome the challenges associated with the poor penetration of traditional external light sources. Recent progress in protein engineering and delivery systems has broadened the scope of bioluminescence in numerous applications, including photodynamic therapy. This review outlines the essential principles of bioluminescence and examines its recent applications in photodynamic therapy for the treatment of cancers. Additionally, it offers insights into future research avenues based on the current studies in bioluminescent systems to further enhance their potential.</p>