Starting in the late 70's Marvel published a book called What If, which explored possible storylines, that broke off from the actual universe's continuity, based on one particular event happening in a different way, or a different choice being made by the characters. In 1998, What If #105, written by Tom DeFalco, who is often credited (or blamed) with the Clone Saga of the Mid-90's, focused on "What If Peter and Mary Jane had raised their baby?". The point at which the book diverges from continuity is where, rather than Peter and Mary Jane Parker's baby daughter 'May' getting kidnapped and dying, she is returned safely to her parents.
Now, 15 years later, May "Mayday" Parker is in high school and, to her parents' concern, is excelling at basketball, clearly developing spider-powers of her own. And then Normie Osborne, the Green Goblin's Grandson, sets out to restore the family name, and May, donning her 'uncle' Ben Reilly's Spider costume to fight him, and continue to fight crime.
The What If book sold well enough for Marvel to create a whole new book, Spider-Girl set in this MC2 (Marvel Comics 2) Universe, to follow the exploits of the "daughter of the true Spider-man."
Approaching a hundred issues, making it Marvel's longest running book with a female lead, and with a creative team that has consistently churned out entertaining issues with smart writing, and great art, Spider-Girlis, in Marvel Editor-in-Chief Joe Quesada's words, "the little book that could". Tom DeFalco who's written almost every issue, gives both the younger audience they're due by keeping it light and all-ages friendly, instead of an over-mature, gritty book that's all too common in the industry these days, and also giving older Marvel fans a reason to keep reading by skillfully introducing in various characters from Spider-Man's past and artists Ron Frenz and Pat Oliffe translate this writing into some great art. At one point of time, the MC2 universe included a few other books featuring the successors to the Avengers, A-Next, the Fantastic Five, and others, but all of these were canceled due to low sales.
And Spider-Girl too hasn't exactly had a free run. Plagued by low sales, Marvel repeatedly canceled the book throughout its lifetime, and every time the small but enthusiastic community of Spider-Girl fans found out, they went up in flames, writing letters to Marvel to save the book, persuading shops to order more copies of it, showing the book to as many people they could and asking them to buy it, and more. At the forefront of this Spider-Girl Blitz was the One, True Spider-Girl Message Board at Comic Boards.com which is often frequented by creator/writer Tom DeFalco himself. DeFalco once said "The grassroots support from the SG message board has been fantastic. Those fans have managed to keep Spider-Girl alive. They never gave up on the title. Not even when Marvel canceled it and told me there was no hope of ever bringing it back. Spider-Girl lives because of her fans!"