This alien species originates from an alternate plane of existence, one of fluidic matter. They were found by the Borg who considered them the pinnacle of organic genetic evolution. When the Borg attempted to assimilate this species they found that Species 8472 was immune to the assimilation nanoprobes the Borg used. Species 8472 also demonstrated powerful telepathic abilities. The space craft emplyed by Species 8472 was biological in nature made from the same genetic material that the aliens were made from.
While conducting an investigation of a destroyed Borg Cube, the U.S.S. Voyager discovered on of the ships attached to a section of the Borg cube. During an away team investigation, Ensign Harry Kim was injured by one of the aliens, causing him to be infected by the aliens DNA. This DNA attempted to convert Ensign Kim's cells into that of the alien species. The Doctor found a way to modify the Borg nanoprobes so that they could neutralize the alien DNA, saving the life of Ensign Kim.
 Forming a temporary alliance with the Borg Collective, Voyager and the Borg were able to manufacture the nanoprobes and a weapons delivery system that was able to stop Species 8472 and force their withdrawl back to fluidic space.