Star Trek: Deep Space Nine (DS9) focuses on the 24th century adventures of Captain Benjamin Sisko on space station Deep Space 9, an outpost situated near the mouth of a stable wormhole on the far reaches of explored space. Although Sisko commands Deep Space 9, the station actually belongs to the inhabitants of nearby Bajor, who requested Starfleet's protective presence after Bajoran freedom fighters put an end to the brutal Cardassian occupation of their world. Approximately a sixth of the station's 300 permanent residents are Starfleet personnel; there is also a sizable Bajoran militia presence. The rest of Deep Space 9's inhabitants are civilians, most of whom work in the station's Promenade, a kind of indoor marketplace. Initially, Sisko's mandate from Starfleet was to protect Bajor and the station from any hostiles who ventured into the area. But with the discovery of the nearby wormhole—a shortcut through space that leads directly to the uncharted Gamma quadrant—Sisko's mandate has expanded exponentially, as the region becomes the gateway to all manner of visitors, both friendly and extremely hostile.

Star Trek: The Next Generation (TNG) focuses on the 24th century adventures of Captain Jean-Luc Picard aboard the U.S.S. Enterprise (NCC-1701-D). This incarnation of the famous starship is much larger than the one captained by James T. Kirk a century earlier, and, accordingly, it carries a larger crew complement: 1,012 men, women…and, surprisingly, children. This era's Starfleet Command believes that men and women are more likely to sign up for long-term exploratory missions if they think of their ship as home. Thus, Picard's crew enjoys many of the comforts they'd have otherwise left behind, including a wide variety of recreational opportunities, "replicated" food dishes to suit every palate, and quarters large enough to share with spouses and offspring. There are schools for the children and a bar (stocked with synthetic alcohol, or synthehol) where the adults can unwind. However, the ongoing mission—no longer limited to a mere five years—remains virtually the same as it was during Kirk's time: to seek out new life and new civilizations, and to boldly go where no one has gone before.

Star Trek: Voyager (VOY) focuses on the 24th century adventures of Captain Kathryn Janeway aboard the U.S.S. Voyager. Smaller than either Kirk's or Picard's starships—its crew complement is only 150—Voyager is fast and powerful, and has the ability to land on a planet's surface. It is one of the most technologically advanced vessels in Starfleet, utilizing computer circuitry that incorporates synthetic neural tissue. Ironically, Janeway's inaugural mission aboard Voyager was to be her last in the Alpha quadrant. While attempting to capture the crew of a renegade Maquis vessel, both her ship and that of the Maquis were pulled into the distant Delta quadrant by powerful alien technology. Unfortunately, there would be no similar "express" route to take them home again. Stranded 70,000 light-years from Earth, Janeway convinced the Maquis to join her Starfleet crew and serve together during the long voyage back to Federation space.

With the help of long presumed dead Captain Kirk, Captain Picard must stop a deranged scientist willing to murder on a planetary scale in order to enter a space matrix.

The Borg travel back in time intent on preventing Earth's first contact with an alien species. Captain Picard and his crew pursue them to ensure that Zefram Cochrane makes his maiden flight reaching warp speed.

When the crew of the Enterprise learn of a Federation conspiracy against the inhabitants of a unique planet, Captain Picard begins an open rebellion.

The Enterprise is diverted to the Romulan homeworld Romulus, supposedly because they want to negotiate a peace treaty. Captain Picard and his crew discover a serious threat to the Federation once Praetor Shinzon plans to attack Earth.

Star Trek: Enterprise (ENT) focuses on the 22nd century adventures of Captain Jonathan Archer aboard the Enterprise NX-01 during the early days of interstellar travel. The NX designation indicates that this Enterprise is an experimental prototype; Unlike the starships of the four other Star Trek series, this Enterprise doesn't have deflector shields or phasers, but it does come equipped with a phase cannon and a rudimentary transporter that functions efficiently most of the time.

The series is set 20 years after Jean-Luc Picard's last appearance in Star Trek: Nemesis (2002), and follows him in the next chapter of his life.