The Atlantis team, along with Weir and now with the ability to make large hyperspace jumps in only a puddle jumper, must now journey to the replicator home planet to steal one of their many ZPMs to bring the city back to life, and finish the journey to their new planet.

The entire city locks down for a false quarantine, leaving people stranded with a decreasing amount of oxygen, while Rodney is unable to reach a computer.

Combat engineers from Atlantis work against the clock to rescue four of their colleagues who are now trapped in the rubble of Michael's medical compound. With Michael en route, they quickly locate McKay and Major Lorne but Sheppard and Ronon are far deeper and their rescue is not assured. When Michael's ship arrives, they decide to try to rescue Teyla who is in labor and close to giving birth. When it's all over, Col. Carter is recalled to Earth for a performance review but Richard Woolsey has some bad news for her.

Dr. Carson Beckett is removed from stasis because he's the only one who can find the antidote to a mysterious virus that has incapacitated base personnel, beginning with Dr. Jennifer Keller.

Rodney is infected with a deadly illness known as "second childhood" which diminishes his mind capabilities and makes him lose his memory gradually.

Teyla risks her life on a daring mission aboard a wraith hive ship.

Dr. Daniel Jackson comes to Atlantis in search of a lost Atlantian room. The discovery reveals a new race. Daniel and McKay are kidnapped by the new race and are forced to finish a device which may kill the Wraith. Todd feels betrayed and takes the Daedalus.

The new race that stole the device, not to mention Rodney and Daniel, turns out to be an old one meaning very old and well known to the human race. With an ancient grudge to settle, they force Rodney to activate the device against the Wraith with a side effect that could kill millions throughout the galaxy. That makes the Wraith mad so they abscond with the Daedalus to retaliate. Once again we lowly humans have to take control of a messy situation to keep the master races from wreaking havoc in the galaxy.

When the power is shut down and most of the inhabitants are locked out of key controls, it is apparent that Atlantis has been taken over by an off-world group, soon identified as Michael and his hybrids. He is after Teyla's newborn child who is key in his quest to gain control of the Pegasus galaxy. While Sheppard and McKay try to get their hands on a jumper to launch an attack, Ronon and others who were taken prisoner by Michael during his initial invasion launch reprisals of their own. When Teyla manages to get away and hide, Michael gives her a simple choice: surrender herself and her child to him or he will use the city's self-destruct mechanism to kill everyone.

Radek discovers an alien device that Rodney finds holds serious surprises. Sheppard runs into a reincarnated Acastus Kolya who plans to attack Atlantis. An IOC representative arrives to replace Woolsey who receives advice from a mysterious woman.

A Wraith cruiser arrives at Atlantis and is strangely uncommunicative.

A hive ship turbo-charged with a ZPM has received the Wraith's message from a alternate universe containing the location of Earth. The ship is now heading for Earth.