H.H. Holmes, originally named Herman Webster Mudget, was the official first serial killer in American history and the main antagonist in the season 2 episode No Exit of Supernatural.
He was played by Stephen Aberie.
He was suspected to have murdered at least two hundred women, luring them to his apartment where he'd torture them before killing, and he used his job as a doctor to torture them and to provide an alibi for his killings.
H.H. Holmes had a profound hatred of women for some reason. He was eventually arrested for serial killings and convicted of only twenty murders. However, he hinted he killed over two hundred women.
In his quarters, he had a house of horrors which included the tortured corpses of all his victims. Holmes was first suspected when police found a forged letter he claimed to have written. He was arrested, and hanged, but before he was, he had one final request.
Before his execution, he wanted to be buried in an elaborate tomb under six feet of concrete, to protect his corpse. He might have known hunters who had told him that vengeful ghosts could only be sent to Hell by burning their remains, and thus the idea of returning as a vengeful ghost was attractive to Holmes. He was hanged, but he came back.
H.H. Holmes returned as a ghost and haunted his apartments around where he used to live. He was an immensely powerful ghost as his mere presence could interfere with electrical devices and he could bleed immense amounts of ectoplasm which other ghosts only did when possessing somebody. Holmes could possess people and he liked scaring women, appearing behind a crack in the wall with his eye glaring at them. He would drag them down to his basement where he'd torture them before killing them.
He killed about five residents of his apartment in this way and all of them were women.
In the episode
When Sam and Dean go to visit an alleged haunted apartment, they find that Jo Harvelle has turned up for the trip. Jo is getting bored at being stuck behind all the time and she wants excitement. However, she gets more than she bargained for when, whilst investigating the flats, she is attacked and abducted by H.H. Holmes.
Sam and Dean panic but they do some research and find the flats were the house of horrors owned by H.H. Holmes and he requested to be buried under several feet of concrete so they cannot dig up his body and burn his bones. They realize they have to face him head on.
They travel to the basement and find an imprisoned Jo who they release. H.H. Holmes is caught off guard, having been lusting after Jo. Sam and Dean manage to spread salt around the entire basement, trapping an enraged Holmes in the prison.
Just to be on the safe side, they fill in the basement with concrete, thus further making sure H.H. Holmes cannot return to cause more chaos.