Chris Claremont made a brief return from #381 (June 2000) to #389, at which point he transferred to the new X-Treme X-Men title, as Grant Morrison took over the X-Men vol. 2 and that became the flagship X-Men title. From 2001 Lobdell made a short return, and then Joe Casey and Chuck Austen wrote runs into 2004. The title became bimonthly from 2003 to 2004.
The X-Men: Reload reshuffle of titles in 2004 led to Claremont returning to Uncanny with issue #444. The stories addressed the new status quo established by Morrison, with Jean Grey having died again, and Cyclops in a relationship with Emma Frost. Claremont remained until #473. His final story was the “Death of the Greys” in 2006, as part of the “Decimation” storyline, where the vast majority of mutants had lost their powers. He was replaced by Ed Brubaker, who wrote a 12-part epic space opera story “The Rise and Fall of the Shi’ar Empire”, as a follow-up to his miniseries X-Men: Deadly Genesis. After this the title led into the “Messiah Complex” crossover event, dealing with the first mutant birth since the Decimation.