Peter Parker is five years old when his parents die. He doesn't know how they die, only that one day he's surrounded by their love and the next, he isn't. He knows that they've already left an indelible mark on his life, on his creative development. And that he's been left to live with his Aunt May and Uncle Ben. He's reminded daily of what he's lost, but that he still has infinitely far to go.
At school, Peter is constantly bullied by Flash Thompson, but school is also the only time he gets to interact with Mary Jane, the girl next door, and play with all the science equipment he wants. He never feels more alive, then. At home, even though Aunt May and Uncle Ben love him, they can't fill the void that was torn from him. He spends most of his time elsewhere. When he reaches high school, Peter is practically invisible, Mary Jane is unobtainable, Flash is incorrigible, and science all Peter knows. When he takes a field trip to a science museum, Peter is accidentally bitten by an irradiated spider, escaped from a nearby lab run by Norman Osborn, who works part-time at the museum.
Discovering that he has comparable abilities to the spider, Peter removes himself from his own head for the first time since he was five. He puts together a costume, and is promptly caught by his Uncle Ben, who violently disapproves. Angrily, he leaves and vows to never return. He sheepishly asks Mary Jane if he can stay at her place for a while, and she surprises him by saying yes! At school, Peter picks a fight with Flash, and gets a suspension. He wanders back to the museum, trying to figure everything out, when he comes across Norman Osborn, whom he confesses most of his problems to. Norman actually agrees to become Peter's mentor!
Things are looking up on average. Aunt May and Uncle Ben suffer an armed burglary in the meantime, which Uncle Ben is able to thwart, but the thief threatens revenge. He tries to talk to Peter about it, in the course of an intended reconciliation, but Peter will have none of it. Peter is, in fact, hanging out with Osborn when the thief makes good on his threat. Shellshocked by the news that his aunt and uncle have been murdered, Peter is even less prepared when he discovers that Osborn may have had something to do with it, thanks to an unlikely friendship with Flash Thompson, who envied Peter's time with Norman, who has always displayed an unstable psyche.
To figure it all out, Peter finally adopts the persona Uncle Ben tried to warn him about - with great power comes great responsibility - and becomes Spider-Man. Once again, life will never be the same.
Juggling his relationship with Mary Jane, his rivalry with Flash Thompson, life as Spider-Man, and the potential that Norman Osborn may be his greatest enemy, Peter Parker also attempts to secure an academic future, and now he'll have to support himself. Finding his father's old camera, he reports to the Daily Bugle as the staff's youngest photographer, armed with the knowledge that he's got New York's biggest story right under his own shirt.