Dwarf irregular (dIrr) galaxies are among the most common type of galaxy in the Universe. They typically have gas-rich, low-surface-brightness, metal-poor, and relatively thick disks. Here, we summarize the current state of our knowledge of the interstellar medium (ISM), including atomic, molecular, and ionized gas, along with their dust properties and metals. We also discuss star-formation feedback, gas accretion, and mergers with other dwarfs that connect the ISM to the circumgalactic and intergalactic media. We highlight one of the most persistent mysteries: the nature of pervasive gas that is yet undetected as either molecular or cold hydrogen, the “dark gas.” Some highlights include the following: ▪Significant quantities of Hi are in far-outer gas disks.▪Cold Hi in dIrrs would be molecular in the Milky Way, making the chemical properties of star-forming clouds significantly different.▪Stellar feedback has a much larger impact in dIrrs than in spiral galaxies.▪The escape fraction of ionizing photons is significant, making dIrrs a plausible source for reionization in the early Universe.▪Observations suggest a significantly higher abundance of hydrogen (H2 or cold Hi) associated with CO in star-forming regions than that traced by the CO alone.