His work included a collaboration with Tim Sale in Tales of the Vampires, and the main story of Superman/Batman #26.

Jeph Loeb's son Sam Loeb died on June 17, 2005 at the age of 17 after a three-year battle with cancer (in his leg, his jaw, and finally his lung) before finishing the story he was writing for Superman/Batman #26. Jeph Loeb, along with 25 other comic book professionals and artists who had known Sam, worked on the issue, scripting or penciling individual pages. Marvel Comics allowed John Cassaday and Joss Whedon to work on the issue despite their exclusive contracts. All 26 contributors donated their fees and royalties for the issue to The Sam Loeb College Scholarship Fund.

In "The Boys Are Back in Town" (issue #26), Superman and Batman send Superboy and Robin to visit the teenage Toyman in Japan because he has not been heard from in a while. The issue was released shortly after Superboy's death in Infinite Crisis #6, and Robin's eulogy of Superboy serves as both a framing sequence and as a meditation on the author's passing.

The 26 contributors to the issue:

"Sam's Story", a back-up story written by Jeph Loeb ten days after his son's death, depicts young Clark Kent's friendship with a boy named Sam who gets cancer. Tim Sale provides the art for the story in a style reminiscent of the Superman For All Seasons limited series.