In 2004, Marvel used the title Astonishing X-Men for the ongoing X-Men series written by Joss Whedon and illustrated by John Cassaday. It is a continuation of Grant Morrison's New X-Men title and features a similar line-up of characters, including Cyclops and Emma Frost (as co-team leaders), Beast, Shadowcat, Colossus, Lockheed and Wolverine. This team became the usual focus for most X-Men limited series from then on as well.
Whedon/Cassaday's Astonishing X-Men introduced a number of original characters into the Marvel Universe including Special Agent Brand, S.W.O.R.D., Hisako Ichiki, Ord of the Breakworld and Blindfold.
The first story arc focused on the introduction of several key characters and their involvement on the team. Whedon introduced a "mutant cure" designed by Indian Benetech scientist Dr. Kavita Rao, who was secretly sponsored by warrior alien Ord. The perspective of "real" humanity aroused a heavily-mutated Beast, who visited Rao where he discovers that the drug is the product of illegal human experimentation on an unknown victim. The X-Men raided Benetech and were reunited with Colossus. With Colossus' help, the team took down Ord, but not before it was revealed that a mutant (most likely an X-Man) would destroy Ord's home planet, — the Breakworld — within the next three years.
With this 2005 arc, Whedon brought in Colossus four years after his comic book death in 2001. The "mutant cure" plot was also base of the X-Men: The Last Stand movie plot. The arc was critically lauded and won the 2006 Will Eisner Award for "Best Continuing Series". IGN called the arc "best X-Men run in a decade" and lauded Whedon for flawless character dynamics.
This Whedon arc features a Sentinel attack with a mystery mastermind. The culprit is the Danger Room, who is becoming sentient and appears as a robot called "Danger". Whedon establishes that Professor X imprisoned Danger and made it an unwilling host of the Danger Room, leaving the X-Men disgusted. Whedon also revealed that Emma Frost is aligned with the newly formed Hellfire Club.
The X-Men are manipulated by a new Hellfire Club, consisting of Cassandra Nova, Emma Frost, the enigmatic Perfection, Negasonic Teenage Warhead, and Sebastian Shaw. Whedon established that Emma Frost is blackmailed into servitude by Cassandra, that the "new" Hellfire Club is only a psychic projection, and that Cyclops's non-control of his optic blasts is result of a childhood trauma. Nova initially beats the X-Men (save Shadowcat) by mind control, but Shadowcat frees her colleagues. At the end, the X-Men fight Nova to a standstill. But before the conflict can be resolved, the X-Men are forcibly teleported away by S.W.O.R.D. to a spaceship headed for the Breakworld.
The final panel of issue 15, in which Shadowcat crouches in a sewer clenching her fists, was an homage to the final panel of Uncanny X-Men #132, in which Wolverine did this gesture.
In the following Unstoppable arc, Whedon wrote an adventure taking place on the alien Breakworld. The X-Men square off against the Breakworld leaders, who are intending to destroy Earth by firing a giant bullet. The Danger subplot is also resolved, and Whedon established that Danger is hard-coded not to kill. In the end, Shadowcat phases inside the Breakworld bullet, and when it reaches Earth, makes it intangible, so that the bullet passes through Earth. Shadowcat seemingly sacrifices her life, comic book death-style.
Marvel announced at San Diego Comicon 2007 that following completion of the Whedon/Cassaday run on Astonishing X-Men, the series would continue with the new creative team of Warren Ellis and Simone Bianchi. This run was expected to debut in early 2008, but was pushed back to July 2008. Ellis and Bianchi's first issue, Astonishing X-Men #25, featured the team relocated to San Francisco, with a base in the Marin headlands. The only addition to the team was Storm. A recent Astonishing X-Men sketchbook was released and showed costume redesigns by Bianchi for the upcoming "Astonishing X-Men: Second Stage". The characters showcased were Dazzler, Beast, Nightcrawler, Archangel, Cyclops, Emma Frost, Colossus, Storm, and Wolverine.
Based in San Francisco, Ellis established the X-Men as protectors of the city. The new team consisted of Cyclops, Emma Frost, Beast, Wolverine and Armor, and later, Storm arrived. The X-Men uncovered a plot of mutant synthesis from an unusual murder. The killer (designated 'X') was located, fixing and restarting the eponymous "ghost box" in a spaceship. X was defeated but killed himself rather than surrender information about his intentions and "the Annex."
The team returned to San Francisco with Suspect X's "mysterious box" aka Ghostbox in tow and gave it to Hank along with a syringe filled with Suspect X's blood. After analyzing the box and blood, Hank told Scott that after having gone over Suspect X's file there appears to be talk about a secret war between Suspect X's people and the murdered mutant from the beginning of the story arc. There is also talk about a mysterious place called Tian which is in China and that piques the interest of Wolverine. After analyzing Suspect X's blood, Hank finds out that Suspect X is just a normal mutant but with his X chromosome in the wrong place. Just like the murder victim, Suspect X is another manufactured mutant. Hank wants to bring in Abigail Brand from S.W.O.R.D. in to help investigate this matter, but Scott is against that. In the end, against Scott's wishes, Agent Brand is brought in who lets the X-Men know that the Ghostbox is a dimensional portal between different realities. Brand wants to turn this case into a S.W.O.R.D.-only case but Scott counters it. Brand gives Scott and the X-Men time to investigate before she brings in S.W.O.R.D. With the help of Wolverine, the X-Men locate Tian, which is an uncharted area of China that no surveillance or satellite system can get through, not even the Chinese government. The X-Men are able to sneak into Tian and discover the headquarters of a group of mutants from another dimension. Sadly, they seem to have died because of the effects of M-Day.
As Storm and Emma investigate the grounded temple, Emma notices they are not alone and that she'll have to switch to her diamond form, leaving her without her telepathy. She relays the info to Cyclops who is with Beast, Armor and Wolverine. As Armor and Logan go off to search the temple for anyone else, Scott and Beast discuss Forge, M-Day and its effects on the multiverse. Armor and Wolverine come across a man who can fire lasers from his fingers, Storm and Emma lose their powers in the presence of the mutant hiding from them and Cyclops and Beast take on a mutant with a strange chameleon mutation. After the X-Men take down their foes, they reveal to the X-Men they have a mutual friend, Forge.
When two of the attacking mutants are defeated, Emma interrogates them and the team discovers that Forge has acquired a Ghost Box and is planning a counter-strike against the Annexation. Cyclops and Storm try to reason with Forge but he reveals his madness, stemming from years of being ignored and neglected and wants to leave behind a legacy and save the world. Beast orders his girlfriend Abigail Brand to send an immensely powerful laser beam into the Ghost Box's portal. Storm urges Forge to escape but he would rather face death than humiliation and the team escapes as the beam destroys both the Ghost Box and the world from whence the invaders came.