A substantial energy barrier of electrostatic forces must be overcome before fusion can occur. At large distances, two naked nuclei repel one another because of the repulsive electrostatic force between their positively charged protons. If two nuclei can be brought close enough together, however, the electrostatic repulsion can be overcome by the quantum effect in which nuclei can tunnel through coulomb forces.
When a nucleon such as a proton or neutron is added to a nucleus, the nuclear force attracts it to all the other nucleons of the nucleus (if the atom is small enough), but primarily to its immediate neighbors due to the short range of the force. The nucleons in the interior of a nucleus have more neighboring nucleons than those on the surface. Since smaller nuclei have a larger surface-area-to-volume ratio, the binding energy per nucleon due to the nuclear force generally increases with the size of the nucleus but approaches a limiting value corresponding to that of a nucleus with a diameter of about four nucleons. It is important to keep in mind that nucleons are quantum objects. So, for example, since two neutrons in a nucleus are identical to each other, the goal of distinguishing one from the other, such as which one is in the interior and which is on the surface, is in fact meaningless, and the inclusion of quantum mechanics is therefore necessary for proper calculations.
The electrostatic force, on the other hand, is an inverse-square force, so a proton added to a nucleus will feel an electrostatic repulsion from all the other protons in the nucleus. The electrostatic energy per nucleon due to the electrostatic force thus increases without limit as nuclei atomic number grows.
The net result of the opposing electrostatic and strong nuclear forces is that the binding energy per nucleon generally increases with increasing size, up to the elements iron and nickel, and then decreases for heavier nuclei. Eventually, the binding energy becomes negative and very heavy nuclei (all with more than 208 nucleons, corresponding to a diameter of about 6 nucleons) are not stable. The four most tightly bound nuclei, in decreasing order of binding energy per nucleon, are , , , and . Even though the nickel isotope, , is more stable, the iron isotope  is an order of magnitude more common. This is due to the fact that there is no easy way for stars to create  through the alpha process.
An exception to this general trend is the helium-4 nucleus, whose binding energy is higher than that of lithium, the next heavier element. This is because protons and neutrons are fermions, which according to the Pauli exclusion principle cannot exist in the same nucleus in exactly the same state. Each proton or neutron's energy state in a nucleus can accommodate both a spin up particle and a spin down particle. Helium-4 has an anomalously large binding energy because its nucleus consists of two protons and two neutrons (it is a doubly magic nucleus), so all four of its nucleons can be in the ground state. Any additional nucleons would have to go into higher energy states.  Indeed, the helium-4 nucleus is so tightly bound that it is commonly treated as a single quantum mechanical particle in nuclear physics, namely, the alpha particle.
The situation is similar if two nuclei are brought together. As they approach each other, all the protons in one nucleus repel all the protons in the other. Not until the two nuclei actually come close enough for long enough so the strong attractive nuclear force can take over and overcome the repulsive electrostatic force. This can also be described as the nuclei overcoming the so-called Coulomb barrier. The kinetic energy to achieve this can be lower than the barrier itself because of quantum tunneling.
The Coulomb barrier is smallest for isotopes of hydrogen, as their nuclei contain only a single positive charge. A diproton is not stable, so neutrons must also be involved, ideally in such a way that a helium nucleus, with its extremely tight binding, is one of the products.
Using deuterium–tritium fuel, the resulting energy barrier is about 0.1 MeV. In comparison, the energy needed to remove an electron from hydrogen is 13.6 eV. The (intermediate) result of the fusion is an unstable He nucleus, which immediately ejects a neutron with 14.1 MeV. The recoil energy of the remaining He nucleus is 3.5 MeV, so the total energy liberated is 17.6 MeV. This is many times more than what was needed to overcome the energy barrier.
The reaction cross section (σ) is a measure of the probability of a fusion reaction as a function of the relative velocity of the two reactant nuclei. If the reactants have a distribution of velocities, e.g. a thermal distribution, then it is useful to perform an average over the distributions of the product of cross-section and velocity. This average is called the reactivity, denoted . The reaction rate (fusions per volume per time) is  times the product of the reactant number densities:
If a species of nuclei is reacting with a nucleus like itself, such as the DD reaction, then the product  must be replaced by .
 increases from virtually zero at room temperatures up to meaningful magnitudes at temperatures of 10–100 keV. At these temperatures, well above typical ionization energies (13.6 eV in the hydrogen case), the fusion reactants exist in a plasma state.
The significance of  as a function of temperature in a device with a particular energy confinement time is found by considering the Lawson criterion.  This is an extremely challenging barrier to overcome on Earth, which explains why fusion research has taken many years to reach the current advanced technical state.