In classical physics, mass was usually identified with the ‘quantity of matter' and this quantity was supposed to be conserved in any physical interaction. In Special Relativity, the concept of mass loses any relationship with the ‘amount' of matter, becoming an abstract measure of inertia. The two classical principles of mass conservation and energy conservation no longer hold. They are replaced by the principle of conservation of mass-energy, a very general one, holding in any physical situation, regardless of the kind of interaction involved. This conceptual revolution and the revision of the classical notion of material particle (see complementarity and indiscernibility) occurred in parallel and gave rise to Quantum Field Theory, the synthesis of quantum theory and Special Relativity.

When undergoing relativistic collisions (i.e. collisions involving velocities close to c), material particles can be converted totally to electromagnetic energy and vice versa. More generally, any modification of a body's rest energy (for example by heating), produces a corresponding change in its mass.

In ordinary situations, the presence of the factor c² in eq. (1) makes this change too tiny to be detected; but there exists concrete examples in which this is not the case. In the explosion of an atomic bomb, the energy released by a few tens of kilos of plutonium is equivalent to a mass as large as 1 gram, corresponding to the huge amount of energy liberated in the explosion.

The equivalence of mass and energy provides the theoretical framework to understand most processes occurring on a cosmological scale, as well as the sub-nuclear phenomena of high energy physics, in which particles appear to be continuously created and annihilated through the fundamental interactions. The design of particle accelerators devoted to the study of these processes must take into account the severe limitations imposed by eq. (2).

The practical consequences of eq. (1) are far-reaching. Following the discovery that even the lightest massive particle provides a huge energy reservoir, a big effort was devoted to implement nuclear manipulations capable to extract and exploit this energy.