The interstellar medium (ISM) is the matter and radiation that exists in the space between the star systems in a galaxy. This matter includes gas in ionic, atomic, and molecular form, as well as dust and cosmic rays. It fills interstellar space and blends smoothly into the surrounding intergalactic medium. The energy that occupies the same volume, in the form of electromagnetic radiation, is the interstellar radiation field. Although the density of atoms in the ISM is usually far below that in the best laboratory vacuums, the mean free path between collisions is short compared to typical interstellar lengths, so on these scales the ISM behaves as a gas (more precisely, as a plasma: it is everywhere at least slightly ionized), responding to electromagnetic radiation, and not as a collection of non-interacting particles.

The interstellar medium is composed of multiple phases distinguished by whether matter is ionic, atomic, or molecular, and the temperature and density of the matter. The interstellar medium is composed primarily of hydrogen, followed by helium with trace amounts of carbon, oxygen, and nitrogen. The thermal pressures of these phases are in rough equilibrium with one another. Magnetic fields and turbulent motions also provide pressure in the ISM, and are typically more important, dynamically, than the thermal pressure. In the interstellar medium, matter is primarily in molecular form and reaches number densities of 10¹² molecules per m³ (1 trillion molecules per m³). In hot, diffuse regions, gas is highly ionized, and the density may be as low as 100 ions per m³. Compare this with a number density of roughly 10²⁵ molecules per m³ for air at sea level, and 10¹⁶ molecules per m³ (10 quadrillion molecules per m³) for a laboratory high-vacuum chamber. Within our galaxy, by mass, 99% of the ISM is gas in any form, and 1% is dust. Of the gas in the ISM, by number 91% of atoms are hydrogen and 8.9% are helium, with 0.1% being atoms of elements heavier than hydrogen or helium, known as "metals" in astronomical parlance. By mass this amounts to 70% hydrogen, 28% helium, and 1.5% heavier elements. The hydrogen and helium are primarily a result of primordial nucleosynthesis, while the heavier elements in the ISM are mostly a result of enrichment (due to stellar nucleosynthesis) in the process of stellar evolution.

The ISM plays a crucial role in astrophysics precisely because of its intermediate role between stellar and galactic scales. Stars form within the densest regions of the ISM, which ultimately contributes to molecular clouds and replenishes the ISM with matter and energy through planetary nebulae, stellar winds, and supernovae. This interplay between stars and the ISM helps determine the rate at which a galaxy depletes its gaseous content, and therefore its lifespan of active star formation.

Voyager 1 reached the ISM on August 25, 2012, making it the first artificial object from Earth to do so. Interstellar plasma and dust will be studied until the estimated mission end date of 2025. Its twin Voyager 2 entered the ISM on November 5, 2018.

Table 1 shows a breakdown of the properties of the components of the ISM of the Milky Way.

Field, Goldsmith & Habing (1969) put forward the static two phase equilibrium model to explain the observed properties of the ISM. Their modeled ISM included a cold dense phase (T < 300 K), consisting of clouds of neutral and molecular hydrogen, and a warm intercloud phase (T ~ 10⁴ K), consisting of rarefied neutral and ionized gas. McKee & Ostriker (1977) added a dynamic third phase that represented the very hot (T ~ 10⁶ K) gas that had been shock heated by supernovae and constituted most of the volume of the ISM. These phases are the temperatures where heating and cooling can reach a stable equilibrium. Their paper formed the basis for further study over the subsequent three decades. However, the relative proportions of the phases and their subdivisions are still not well understood.

The basic physics behind these phases can be understood through the behaviour of hydrogen, since this is by far the largest constituent of the ISM. The different phases are roughly in pressure balance over most of the Galactic disk, since regions of excess pressure will expand and cool, and likewise under-pressure regions will be compressed and heated. Therefore, since P = n k T, hot regions (high T) generally have low particle number density n. Coronal gas has low enough density that collisions between particles are rare and so little radiation is produced, hence there is little loss of energy and the temperature can stay high for periods of hundreds of millions of years. In contrast, once the temperature falls to O(10⁵ K) with correspondingly higher density, protons and electrons can recombine to form hydrogen atoms, emitting photons which take energy out of the gas, leading to runaway cooling. Left to itself this would produce the warm neutral medium. However, OB stars are so hot that some of their photons have energy greater than the Lyman limit, E > 13.6 eV, enough to ionize hydrogen. Such photons will be absorbed by, and ionize, any neutral hydrogen atom they encounter, setting up a dynamic equilibrium between ionization and recombination such that gas close enough to OB stars is almost entirely ionized, with temperature around 8000 K (unless already in the coronal phase), until the distance where all the ionizing photons are used up. This ionization front marks the boundary between the Warm ionized and Warm neutral medium.

OB stars, and also cooler ones, produce many more photons with energies below the Lyman limit, which pass through the ionized region almost unabsorbed. Some of these have high enough energy (> 11.3 eV) to ionize carbon atoms, creating a C II ("ionized carbon") region outside the (hydrogen) ionization front. In dense regions this may also be limited in size by the availability of photons, but often such photons can penetrate throughout the neutral phase and only get absorbed in the outer layers of molecular clouds. Photons with E > 4 eV or so can break up molecules such as H₂ and CO, creating a photodissociation region (PDR) which is more or less equivalent to the Warm neutral medium. These processes contribute to the heating of the WNM. The distinction between Warm and Cold neutral medium is again due to a range of temperature/density in which runaway cooling occurs.