 In this entry, we have presented the physics of mass-energy equivalence as widely understood by both physicists and philosophers. We have also canvassed a variety of philosophical interpretations of mass-energy equivalence. Along the way, we have presented the merits and demerits of each interpretation. We have also presented a brief history of derivations of mass-energy equivalence to emphasize that the equivalence of mass and energy is a direct result to changes to the structure of spacetime imposed by special relativity. Finally, we have briefly and rather selectively discussed the empirical confirmation of mass-energy equivalence.