The musical opens in the workhouse, as the half-starved orphan boys are entering the enormous lunchroom for dinner. ("Food Glorious Food") They are fed only gruel. Nine year old Oliver Twist gathers up the courage to ask for more. He is immediately apprehended and is told to gather his belongings by Mr Bumble and the Widow Corney, the heartless and greedy caretakers of the workhouse ("Oliver!"). Mr Bumble and Widow Corney start flirting during conversation. Mr Bumble goes too far in "I Shall Scream!". At the end, Widow Corney ends up on Mr Bumble's lap, kissing him. Oliver comes back and is promptly sold ("Boy for Sale") and apprenticed to an undertaker, Mr. Sowerberry. He and his wife taunt Oliver with the song "That's Your Funeral". He is sent to sleep in the basement with the coffins, something which makes him visibly uncomfortable. ("Where is Love?").
The next morning bully Noah Claypole, who oversees Oliver's work, badmouths Oliver's dead mother, whereupon Oliver begins pummeling him. Mr. Bumble is sent for, and he and the Sowerberrys lock Oliver in a coffin, but during all the commotion Oliver escapes and runs away to London, where his father used to live. On his first day there, he meets the Artful Dodger, a boy wearing an oversize coat and a top hat. He beckons Oliver to join him with "Consider Yourself". Dodger is, unknown to Oliver, a boy pickpocket, and he invites Oliver to come and live in Fagin's lair. Fagin is a criminal, and he is in the business of teaching young boys to pick pockets. Oliver, however, is completely unaware of any criminality, and believes that the boys make handkerchiefs rather than steal them. Oliver is introduced to Fagin and all the other boy pickpockets, and is taught their ways in "You've got to Pick a Pocket or Two".
The next day, Oliver meets Nancy, the live-in girlfriend of the evil, terrifying Bill Sikes, a burglar whose abuse she endures because she loves him. Nancy and Oliver take an instant liking to each other, and Nancy shows motherly affection toward him. Bet, Nancy's younger sister (merely her best friend in the 1968 film and in Dickens' novel), is also with her. Nancy, along with Bet and the boys, sing about how they don't mind a bit of danger in "It's a Fine Life". Dodger humorously starts pretending to be an upper-class citizen, ("I'd Do Anything"), along with Fagin, Oliver, Nancy, Bet, and the boys mocking high society. Nancy and Bet leave and Oliver is sent out with the other boys on his first pickpocketing job ("Be Back Soon"), though he still believes that they are going to teach him how to make handkerchiefs. The Dodger, another boy pickpocket named Charley Bates, and Oliver decide to stick together, and when Dodger and Charley rob Mr. Brownlow, a wealthy old man, they run off, leaving the shocked Oliver, who now realizes that his new friends are pickpockets, to be blamed for looking guilty. Brownlow thinks that Oliver is the thief, but Oliver is cleared in court (offstage).
To make up for his error, the wealthy Brownlow has taken Oliver to live with him, noticing something vaguely familiar about him. In the evening the bar is full of people having a good time and Nancy is called upon to sing an old tavern song ("Oom Pah Pah"). Bill Sikes enters and sings ("My Name"), and gets the crowd to leave. Dodger runs in and tells Fagin about Oliver being captured. Fagin and Bill decide that they have to kidnap Oliver to keep him from revealing their whereabouts and secrets. Nancy is asked to participate, but feeling sorry for the boy and wishing him to have a better life if he has the chance - refuses, until Bill slaps her around. She tries to convince herself that he really loves her and expresses her feeling for him in "As Long As He Needs Me".
Meanwhile the next morning, at Mr. Brownlow's house, Ms. Bedwin, the housekeeper, sings Oliver a reprise of "Where is Love?" and as he wakes up they take notice of the street vendors outside in the song "Who Will Buy?". Mr. Brownlow and Dr. Grimwig discuss Oliver's condition. They come to the conclusion that he is fine and that he can return some books to the bookseller for Mr. Brownlow. The Vendors continue to sing ("Who Will Buy") and at the very end, Nancy and Bill show up and grab Oliver. They bring him back to Fagin's, where Nancy saves Oliver from a beating from Sikes after the boy tries to flee but is stopped. Nancy angrily and remorsefully reviews what their "Fine Life" has come to in "It's A Fine Life (reprise)". When Sikes and Nancy leave, Fagin ponders his future in the humorous song "Reviewing the Situation", in which, every time he thinks of a good reason for going straight, he reconsiders and decides to remain a criminal.
Back at the workhouse, Mr. Bumble and the Widow Corney, now unhappily married, meet up with the dying pauper Old Sally and another old lady, who tell them of how Oliver's mother came to the workhouse to have her baby and gave her a gold locket after the birth, implying that she came from a rich family. The mother then died. Mr Bumble and Widow Corney, realizing that Oliver may have wealthy relatives, visit Mr. Brownlow in order to profit from any reward given out for information of him ("Oliver! (reprise)"). He throws them out, knowing that they have suppressed evidence until they could get a reward for it. Brownlow looks at the picture inside the locket, a picture of his friend's daughter, and realizes that Oliver, who knows nothing of his family history, is actually his grandson. (Oliver's mother had disappeared after having been left pregnant by her lover, who jilted her.)
Nancy, terrified for Oliver and feeling guilty, visits Brownlow and promises to deliver Oliver to him safely that night at midnight on London Bridge - if Brownlow does not bring the police or ask any questions. She then ponders again about Bill in "As Long As He Needs Me (reprise)". Bill suspects that Nancy is up to something. That night, he follows her as she sneaks Oliver out, although in the stage version it is never made clear how he knew exactly when to do this. At London Bridge, he confronts them, knocks Oliver temporarily unconscious, and brutally clubs Nancy to death (in some stagings of the show, he strangles her or slits her throat, but the musical's original libretto follows Dickens's original novel in having her beaten to death). He then grabs Oliver, who has since revived, and runs offstage with him, presumably back to the hideout to ask Fagin for getaway money. Mr. Brownlow, who had been late keeping the appointment, arrives and discovers Nancy's body. A large crowd soon forms, among them the distraught Bet. Bullseye, Bill's fierce terrier, returns to the scene of the crime and the crowd prepares to follow him to the hideout. After they exit Fagin and his boys, terrified at the idea of being apprehended, leave their hideout in panic. Not finding Bill at the hideout, the anxious crowd, now whipped up into a thirst for justice, returns to the Thames Embankment, when suddenly Bill appears at the top of the bridge, holding Oliver as hostage and threatening to kill him if the crowd tries to take him. Unseen by Bill, two policemen sneak up on him. One of them shoots Bill to death and the other grabs Oliver as Bill releases him. Oliver is then reunited with Mr. Brownlow.
After the crowd disperses, Fagin re-enters, making sure not to be seen by anyone, and sings a reprise of "Reviewing the Situation". All of the cast re-enter for curtain calls, singing a medley of "Food Glorious Food" and "Consider Yourself", and then the fourth wall of drama is broken, as the actors respectively playing the supposed-to-be dead Nancy and Sikes re-enter very much alive, and Oliver, joined by the rest of the cast, once more sings to Nancy "I'd Do Anything".
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