In physical theories prior to that of special relativity, mass and energy were viewed as distinct entities. Furthermore, the energy of a body at rest could be assigned an arbitrary value. In special relativity, however, the energy of a body at rest is determined to be mc². Thus, each body of rest mass m possesses mc² of “rest energy,” which potentially is available for conversion to other forms of energy. The mass-energy relation, moreover, implies that if energy is released from the body as a result of such a conversion, then the rest mass of the body will decrease. Such a conversion of rest energy to other forms of energy occurs in ordinary chemical reactions, but much larger conversions occur in nuclear reactions (nuclear reaction). This is particularly true in the case of nuclear-fusion reactions that transform hydrogen to helium, in which 0.7 percent of the original rest energy of the hydrogen is converted to other forms of energy.

Although the atomic bomb proved that vast amounts of energy could be liberated from the atom, it did not demonstrate the precision of Einstein's equation. As knowledge of the atom developed in the 20th century, it was discovered that the protons (proton) and neutrons (neutron) that form its nucleus are themselves formed from the more elementary subatomic particles (subatomic particle) known as quarks (quark), bound together by massless gluons (gluon), in the theory of quantum chromodynamics. However, quarks account for only about 5 percent of an atom's mass (atomic mass), leaving the vast remainder of its mass to be explained. In 2008, following intense computations led by Laurent Lellouch of France's Centre for Theoretical Physics on various supercomputers (supercomputer), the missing mass was shown to reside in the energy associated with the subatomic particles' motions and interactions—in other words, Einstein's equation was verified at the subatomic scale.