In November 2008, Joe Quesada confirmed on his blog that cult favourite Spider-Girl would be moving to Amazing Spider-Man Family in April 2009.

[citation needed] The series took place in the MC2 universe, and bridges the gap between the final issues of DeFalco's run on The Amazing Spider-Man and his future canon in Spider-Girl, taking place shortly after the renegade clone Kaine rescued an infant "Mayday" Parker from the clutches of Norman Osborn's agents and returned her safely to her parents Peter and Mary Jane.

Peter continues his career as Spider-Man and begins to cope with the additional headaches of raising an infant daughter with his wife.

Mayday is six months old when the series begins, and is two when Peter loses his leg in a final battle with the Green Goblin, ending his career as Spider-Man.

[citation needed] The strip was originally intended to run in the closing issue of the Spider-Man Family volume, but was held back to launch within the rebranded title.