Curt Connors was a gifted surgeon who went into a war to help his country. He performed "meatball" surgery on wounded GIs, but his arm was injured in a blast and had to be amputated. He eventually became obsessed with uncovering the secrets of reptilian regeneration, and studied reptilian biology extensively. From his home in the Everglades, he finally determined a serum taken from the DNA of a reptile. He had successfully regrown the missing limb of a rabbit, and, despite the warnings of his wife, chose to test it on himself. Connors ingested it, and his arm did indeed grow back. Unfortunately, it had one side effect: Connors was subsequently transformed into a reptilian monster!
Spider-Man learned about this and travelled to Florida, helping the doctor by using Connors' notes to invent a serum to cure him. Later, Connors was able to repay Spider-Man by developing a formula to save May Parker's life after Peter Parker gave his aunt his radioactive blood during a transfusion that had put May in mortal peril.
For a time, Peter Parker worked as a teaching assistant to Connors. The success of Connors apparent cure from the Lizard personae was short-lived. A repeating pattern occurred: stress or a chemical reaction turned Connors into the Lizard, Spider-Man would fight him, form some kind of temporary cure to revert the transformation, until the next transformation would begin the cycle again.
Over time, it became apparent that a second personality had formed with the Lizard, one with the nigh-impossible goal shared by many villains of taking over the world. Eventually his resorts to using an army of lizards stopped and he began working alone. When his wife and son separated from him (due to the marital strain transforming into a Lizard may cause), Connors tried unsuccessfully to straighten out his life. In despair, The Lizard took control, though it had a weak mental strength, causing the voodoo from Calypso to affect him for her own purposes. After a series of bloody battles, the Lizard and Calypso were defeated by Spider-Man, causing Connors to gain control of his bestial mind. Although it was very weak, the suppressed Connors persona carried out a plan and cured himself, but only temporarily.
For a time, a huge animalistic Lizard appeared, showing up in many issues, causing everyone to believe the Lizard persona was now permanent. However, when this second Lizard went after Connors, Curt drank the old serum to become the true Lizard once again, and save his son's life. The original Lizard returned and killed the second beast, though it also brought the Lizard persona back into action. Later, it was discovered that this new Lizard was an accident from Connors' latest attempt to cure himself. A new formula was tested on a piece of the Lizard's tail, which grew into a fully-formed second creature. Curt and his wife reunited.
One of the Lizard's latest scheme to take over the world had him affecting the water supply to turn everyone into his mindless slaves, though after Connors' son, Billy, almost became one of these zombies, Spider-Man lashed out and attacked the Lizard. After Martha got her share of words in, the Lizard became Connors once again, now begging for help for a cure.
Though reunited with his family, and his missing arm restored by Hammerhead, tragedy struck again in the Connors family - this time, for Martha and Billy. Both mother and son were diagnosed with cancer after years exposed to carcinogens from living near an industrial lab of the Monnano Corporation in Florida. Adding to the tragedy, Curt's new arm degenerated and became useless. Spider-Man assisted Curt, and successfully forced the Monnano Corp. to admit their environmental culpability. However, Martha succumbed to the cancer. Billy survived, and remains bitter towards his father.
With Billy under Curt's sister's care, a darker, mentally-unstable Connors recently revealed a horrible truth to Spider-Man. Curt had returned to New York in search of a research grant. But when the grant was awarded to another scientist named Eric Richardson, Connors blew up the laboratory, and left his rival badly injured. The Lizard was seen leaving the lab, but Connors convinced Spider-Man of his innocence. However, Curt allowed Spider-Man to lock him inside an abandoned vault in the sewers for everyone's safety. Meanwhile, the Daily Bugle obtained a videotape of the transformation, and publicly exposed the truth that the Lizard is the result of a transformation. Spider-Man went to discuss the latest news with Connors in the vault, but the Lizard persona broke free again. Now, Spider-Man learned the truth - Connors admitted he had been lying - he had been in control of the Lizard for some time, and was using his transformation as an escape mechanism to do horrible things. The Lizard escaped, battering Spider-Man into unconsciousness. After confronting Billy, the Lizard was shaken-up with internal conflict. As Connors, he allowed himself to be easily arrested for a bank robbery and locked up to protect those he loves.
The Green Goblin (Norman Osborn) recently freed the Lizard from prison, enhanced his powers to include violence-producing pheromone secretion, and brokered a deal for the creature to join the very short lived Sinister Twelve. The Twelve failed in an attack against Spider-Man and the Black Cat, after the two broke Osborn out of prison. They were defeated by the assistance of the Fantastic Four and other super-powered allies of Spidey. Most recently, the Lizard has resurfaced to face Spidey with the aid of a pint-sized "twin" of himself--who was revealed to be none other than his son, Billy, finally transformed by his father into the new Lizard. Tragically, however, Billy Connors was shot by a resident of the apartment complex upon which Spider-Man and the Black Cat were fighting them. His condition remains grave, and Curtis himself has escaped to the relative safety of the sewers.