The Atlantis expedition must turn to an old friend for help as the Asurans prepare to invade the city.

The IOA is conducting interviews back on Earth to ensure that any personnel serving on Atlantis (in particular, aliens) are suitable for their roles. The episode opens up with a pregnant Teyla having been interviewed and reporting back to Atlantis. Ronon is next. Col. Carter is unsure about Ronon's ability to handle the IOA's interview and therefore asks Teal'c to come to Atlantis in a coaching capacity for Ronon. After a rocky start to their relationship, Ronon and Teal'c return to Earth, via the series of Stargates and a Midway Station, that McKay had previously designed. The Midway Station between the Milky Way and Pegasus galaxies serves primarily as a place for those traveling between the galaxies to serve a 24 hour quarantine. While Teal'c and Ronon are serving their quarantine in the extremely cramped Midway Station, it is boarded by the Wraith, via the Stargate, with the intention to travel to Stargate Command on Earth. They achieve this objective, but only with Teal'c and Ronon in tow. What ensues is a battle between the Wraith and the duo of Teal'c and Ronon, for control of Stargate Command.

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.

The Atlantis team endeavors to thwart Wraith plans to either find a cure for the Hoffan drug (which makes humans deadly to Wraith feeding on them) or exterminate all those infected.