Madison resided in San Francisco, California. She worked as the secretary of a lawyer named Nate Mulligan.
About a month before the events of Heart, Madison was bitten by a werewolf - her next-door neighbor, Glen, who secretly had a crush on her. However, she did not recognize Glen as the culprit and believed the incident to have been a mugging, unaware of the fact that she had been turned into a werewolf by the bite.
Madison had a boyfriend, Kurt Mueller, who was (according to her) possessive, controlling and violent; he almost cost her her job when he punched Nate. After getting bitten, she ended her relationship with Kurt. She later told Sam Winchester that getting "mugged" was the best thing that could have happened to her, as it gave her the strength to take control of her life. However, she was frightened by Kurt's obsessive fixation on her after their break-up.
When Madison fell asleep as a human, she became a werewolf and acted on instinct until her conscious mind reasserted itself. She would kill those her subconscious perceived as a threat; this was seen when she did not attack Sam even though he was in close proximity and asleep at the time her transformation occurred. Upon reverting to human form, she did not remember what she had done as a werewolf.
While transformed, Madison killed Nate. She was then the first to discover his corpse the next morning and was interviewed by hunters Sam and Dean Winchester. She later killed a police officer unlucky enough to encounter her while she was transformed.
The Winchesters came to suspect that Kurt was their culprit and decided that Madison needed to be protected while they investigated him; they played a game of rock, paper, scissors to determine who would stay behind to guard the "hot chick", which Sam won. Madison and Sam were attracted to each other, but they spent the evening watching All My Children on TV.
That night, Madison transformed and, unnoticed by Sam, left her apartment. She killed Kurt but in the process exposed her true nature to Dean, who cut her arm with a silver knife, a wound that remained when she returned to human form. Sam restrained her but her tears and pleading affected him.
Sam and Dean began trying to cure Madison of her lycanthropy by testing their father John's theory that werewolves could be cured by killing the werewolf that had turned them (a theory later proven false). They tracked down and killed Glen. After Madison failed to turn that night because she did not go to sleep, she and the Winchesters believed she was cured. When she fell asleep with Sam, she transformed and escaped.
The next day, Madison realized she was still a werewolf and probably could not be cured. Helpless but resigned to her fate, she asked Sam to kill her because she didn't want to live as a monster killing innocent people. When there appeared to be no other alternative, Sam cried and did as she asked despite Dean's offer to do it instead.
- In It's a Terrible Life, Sam believes that she is his fiancée, suggesting that he still thinks about her. When he tries to call her, the number redirects to (ironically) an animal hospital.
- Season 4