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Stargate Atlantis follows the present-day adventures of Lt. Colonel John Sheppard and his military team from Earth that, along with two dozen other teams, explore distant planets in the Pegasus Galaxy. They use an alien device known as a Stargate that was built millions of years ago by an advanced race of humans known as the Ancients. The expedition is based in the Lost City of Atlantis on the planet "Lantea". The city was built millions of years ago and abandoned 10,000 years ago by the Ancients. Five to ten million years ago, due to a plague in the Milky Way Galaxy, they were forced to flee to the Pegasus Galaxy, and there they seeded life on hundreds of worlds as they had done to Earth in the Milky Way. After encountering a powerful enemy known as the Wraith and going to war with them for one hundred years, the Ancients ultimately lost and were forced to submerge their city beneath Lantea's ocean, which, in the Stargate universe, is the source of the Greek myth of the Lost City of Atlantis.

Stargate: Atlantis episodes feature a self-contained story that also contributes to the larger storyline of the war against the Wraith and the Atlantis residents' search for the means to destroy their enemy. Each season has also featured a two-part episode, and some episodes that, while not technically two-parters, feature direct continuity with the story of the previous episode (for example, season 3 "Progeny" and "The Real World"). Each episode begins with a cold open, sometimes preceded by a recap of events relevant to the upcoming narrative. The opening credits feature an original theme by Joel Goldsmith. Though they were drastically cut at the start of season 2, the full credits were recovered after the mid-season two-parter. They were again cut short in the 5th season.

Season three premiered in the United States on July 14, 2006, picking up where season 2 ended. Having stopped the Wraith from reaching Earth and having failed to develop a working Wraith retrovirus, the expedition faces its third year in the Pegasus galaxy with the Wraith still a threat and a new, powerful enemy bent on destroying the expedition and Atlantis: the Asurans, self-replicating nanobots, also known as Replicators. The situation becomes complicated when an experiment gone awry drains their only ZPM, leaving them without a power source for the city's shields. Soon thereafter, they find a lost Ancient vessel and subsequently lose the city of Atlantis when the crew of the Ancient ship reclaims it. The SGC sends General O'Neill and Richard Woolsey to try to negotiate an agreement between Earth and the Ancients to allow the expedition to return to Atlantis. O'Neill and Woolsey dial Earth and inform them that the Asurans are taking over the city. They kill the Ancient crew who reclaimed the city after 10,000 years. The main members of the Atlantis expedition on Earth disobey their orders and go back to the city, rescue O'Neill and Woolsey, and repel the Asuran invasion. The season finale starts off with Earth launching a first strike against the Asurans, who are building an armada to attack Earth. The Asurans counterattack by attacking Atlantis with a powerful beam weapon fired through a satellite housing a Stargate. As a last resort, the Atlantis team fires up the city's stardrive and escapes into space. The finale ends when the hyperdrive malfunctions, leaving the city flying through uncharted space with a day's worth of energy left in their sole ZPM and Dr. Weir critically injured.

In the fifth season, Richard Woolsey replaces Carter as the leader of the expedition. Teyla, who was held captive by Michael, gives birth to Torren John and escapes with her team, before they are able to cripple Michael. Eventually, he invades Atlantis with a commandeered Puddle Jumper to take Torren and destroy Atlantis but, thanks to the efforts of Sheppard, Teyla, and McKay, Michael is finally killed. The season also introduces a group of rogue Asgard, who unlike their Ida counterparts, actually experiment on humans to prolong their lives, and steal a device known as "The Attero device" to destroy the Wraith, though the side effect is that any Stargate activated after the device has been turned on will explode. The device is eventually destroyed. With the Attero device, Michael and the Hoffan drug, the Wraith have become weakened, and are no longer the power of the galaxy they once were; the falling gives the humans freedom enough to establish a coalition. McKay falls in love with Keller, who eventually reciprocates his feelings, and they become romantically involved. In the finale, Todd the Wraith alerts Atlantis to the fact that an underling wraith possesses a Hive Ship powered by a ZPM. In the process of trying to retrieve the ZPM and disable the Hive, the Atlantis team is present when the Hive receives a communication sent from an alternate reality giving away Earth's location. The Hive disables both the Daedalus and the Apollo, then heads straight to Earth. Thanks to the efforts of the expedition, the ship is finally destroyed over Earth, and Atlantis lands in the Pacific Ocean near the Golden Gate Bridge in San Francisco.

Each season of Stargate Atlantis featured 20 episodes, and in the United States they are broadcast in two series of 10 episodes. The first 10 episodes air from mid-July to September in the United States, ending in the cliffhanger of a two-parter episode. The second half airs first in Canada, from November to January, ending also with a cliffhanger. In the United States, the second half aired from January to March during seasons 1 and 2, but season 3 aired from April to June 2007. Because of the offset, the show has often been bootlegged by American viewers.

   
 

Mallozzi called the Atlantis film Project Twilight until the title of the first Atlantis film was revealed as Stargate: Extinction in late May 2009.Andy Mikita was going to direct the first Atlantis film. The tentative shoot-date of the movie was bound for late 2009 (a date now passed), though there are as yet no details on the release date. As of May 2009, the confirmed actors were to be Amanda Tapping as Samantha Carter, David Hewlett as Rodney McKay, Joe Flanigan as John Sheppard, Paul McGillion as Carson Beckett, Rachel Luttrell as Teyla Emmagan, Jason Momoa as Ronon Dex, Robert Picardo as Richard Woolsey and Christopher Heyerdahl as Todd the Wraith.

The script for Stargate: Extinction had been written and was ready to go into production, according to Joseph Mallozzi, "it involved a return mission to Pegasus, the tragic end of one relationship, the beginning of another, and a surprising progression in the alliance between one man and one wraith." The project however was on hold due to financial troubles at MGM and in the wider economy. In the meantime, an episode of Stargate Universe featuring Atlantis character Rodney McKay was filmed.

On April 17, 2011, Stargate writer and executive producer Brad Wright confirmed that the proposed Stargate Atlantis movie has been indefinitely shelved