A sophisticated lifeform native to a realm of fluidic space a dimension apart from our universe, known only by its Borg designation because its self-ascribed name is unknown. Species 8472 has an extremely dense genetic structure and an extraordinarily powerful immune system; almost anything that penetrates their cells is instantly destroyed, including chemical, biological or technological intruders.

In 2373 the Borg somehow discovered fluidic space and learned that Species 8472 possesses organic spacecraft and a biogenically engineered weapons technology that was superior to anything known to the Borg. Seeking to assimilate this civilization and its technology, the Borg launched an attack on the fluidic space realm, only to be repulsed. Shortly thereafter, Species 8472 launched a retaliatory strike, sending hundreds of powerful bioships into the Delta Quadrant with the goal of eliminating all lifeforms from the galaxy, destroying entire planets and fleets in Borg-occupied space. The 8472 assault was halted when the U.S.S. Voyager collaborated with the Borg to use new nanoprobe technology the crew had developed, a weapon against which the species had no effective defense. It was in the midst of the 8472 battle that Seven of Nine came aboard Voyager and was later severed from the Hive.

Species 8472 considered humanoid genetics to be impure and felt deeply threatened by the violent tendencies of many humanoid cultures. Taking Voyager's alliance with the Borg in 2374 as evidence that Alpha Quadrant powers were planning a devastating attack into fluidic space, Species 8472 sought to infiltrate Starfleet in order gather detailed intelligence and monitor military installations. In preparation for this reconnaissance mission, they constructed a series of "terraspheres" containing elaborate re-creations of key Alpha Quadrant locales, including Starfleet Headquarters, in order to train their operatives in humanoid culture, values and biology. Some of their fears were allayed in 2375 when Voyager's Captain Janeway conducted negotiations with 8472 representatives, the first real talks between the two cultures. Janeway agreed to share her nanoprobe weapons technology with them, in exchange for some of their own technology and a promise to drop their infiltration plans and return to fluidic space.