The TARDIS materializes in a street and the Doctor tells Amy they need to find van Gogh, get him to take them to the church, and then overcome the monster from the painting. Amy asks where the artist might be and the Doctor suggests an orange coloured cafe like the one represented in a painting in the book of van Gogh's work she is carrying. They find the cafe in the next street and ask the owner about van Gogh. He makes a dismissive reply and walks away so the Doctor turns his attention to the waitresses. They say that van Gogh is a drunk who never pays his bills and has no talent.
Van Gogh and the cafe owner emerge. The artist is trying to sell a painting for one Franc so that he can buy another drink but the offer is rejected. The Doctor tries to buy the artist a drink or, failing that, the painting. Van Gogh tells the Doctor that he needs to know three things: he pays for his own drinks, no one buys his paintings or they will be laughed out of town and that Amy is cute. Amy intervenes, ordering a bottle of wine that she will share with whoever she wishes. The Doctor and Amy talk with van Gogh but when the Doctor introduces himself van Gogh assumes that he is a doctor sent by his brother. Amy looks at one of the paintings that van Gogh has with him and lets slip that it is one of her favourites. He is puzzled: she cannot have seen it before. To cover up her mistake she begins flirting with the artist until the Doctor interrupts and asks Vincent if he has painted any churches recently. Van Gogh tells him that he has been waiting for the right weather before painting one church. A woman arrives, screaming for help and the Doctor, Amy and Vincent rush after her.
They find a dead girl lying in the street. The girl's mother blames Vincent's madness for her daughter's death. She and the crowd that has gathered throw stones at Vincent, so the Doctor, Amy and he run away. The Doctor asks if any other murders have taken place and Vincent says that there was one a week earlier. Vincent asks where the Doctor and Amy are staying and the Doctor takes this as an invitation to stay with the artist.
Inside van Gogh's residence the Doctor and Amy are overcome to see so many of his paintings lying about. Van Gogh apologises for 'the clutter' and promises to clear them away some day. The Doctor tells him to be careful with his paintings because they are precious. When the painter asks who thinks that they are precious, Amy says they are precious to her. The Doctor tries to ask about the church but begins to tell him about how he sees the world, that it offers much more than the normal eye can see. He talks about colours; how he can hear them. Amy screams from outside.
Vincent and the Doctor find Amy on the ground, saying that she was knocked over by an unseen assailant. Vincent runs to get a pitchfork and runs towards them, telling them to run The Doctor thinks that Vincent is having a fit. Something knocks him over and he realises that Vincent is fighting an invisible enemy. The Doctor swings a stick around randomly while Vincent drives the creature away.
The Doctor tells Vincent that the creature is invisible to them so Vincent paints over one of his completed canvases, to the Doctor and Amy's distress. The Doctor takes the sketch and tells Amy to keep Vincent safe. He returns to the TARDIS and retrieves a device from a box. It has a scanner that can identify species visually. He tests it on himself (it prints out pictures of his first and second incarnations) but it cannot identify the monster from van Gogh's sketch. The Doctor steps out of the TARDIS and the machine shows the alien behind him. It identifies it as a Krafayis. The Doctor runs and hides until the creature gives up the chase. Amy suddenly appears, both of them scream, and she says that she was bored of Vincent's snoring.
The Doctor wakes Vincent and tells him that Amy has brought him a present for saving her in the night; the house is surrounded by sunflowers. Amy suggests he does a painting of sunflowers but Vincent says that they are not his favourites - to him they are a complex mix of the half-living and half-dying - a challenge. The Doctor tells Vincent he can rise to the challenge.
The Doctor shows Vincent a picture of the Krafayis. He says that they are a pack animal that travels through space. If one of them is lost or left behind the others will not return for it. This one has been left behind, and will kill until it is killed, which is difficult due to the creatures' invisibility. The Doctor says they can fight this creature: if Vincent paints the church the alien will come. Vincent consents to help. Once he has left the room the Doctor tells Amy that, if Vincent is killed, many of the paintings in the Musée d'Orsay will never have existed.
The Doctor finds Vincent on his bed, crying. Vincent says that he knows the Doctor and Amy will leave him; everyone leaves him. The Doctor insists that there is always hope, but Vincent will not be comforted. He becomes annoyed and orders the Doctor to leave. The Doctor explains to Amy that Vincent will soon shoot himself, and they should leave. He says that they should go to the church alone and hope that the Krafayis turns up but Vincent enters, ready to go with them.
Amy walks with Vincent. On the way she tries to say how sorry she is that he feels so sad but he says that he will try to be strong and get through his depression if she can get through hers. She tells him that she is not sad but he says that he can hear it in her: he points out that she is crying.
The Doctor tries to interrupt by suggesting a plan of action. He says that his excellent, if smelly, godmother gave him the device that will allow him to see the monster. On the way, they see the funeral of the girl who was killed the previous night. Vincent sets up his equipment outside the church and begins to paint. After a lengthy period of painting the creature appears in the window of the church. The Doctor goes in, telling Amy and Vincent not to follow but Amy tells Vincent that she will when the time comes.
The Doctor puts on his machine to track the Krafayis. Night falls. Vincent tells Amy that the Krafayis has moved and she rushes inside the church just as the Doctor is knocked to the floor. They hide in a confessional booth until Vincent wards off the Krafayis with a chair, allowing all three of them to escape outside. The Doctor tries to stun the Krafayis with his screwdriver but fails. As the monster attacks Vincent uses the legs of his easel to stab it do death. Vincent says he didn't mean to kill the creature while the Doctor comforts it as it dies.
Later, the three of them lie in a field and look up at the stars while Vincent describes the night sky as he sees it.
The next morning, the Doctor takes Vincent to the TARDIS, now plastered with advertising posters. They show him the inside and then take him to Paris 2010, the Musée d'Orsay. They make their way up to the van Gogh exhibition. The Doctor asks Dr. Black to explain van Gogh's place in of the history of art. Black gives his opinion that he was the finest painter of all, "not only the world's greatest artist but also one of the greatest men of all time." Vincent begins to cry tears of joy before hugging Dr. Black. The Doctor returns Vincent to his own time. Vincent tells the Doctor that he will be a new man from now on and proposes, only partly humorously, to Amy who says she is not the marrying kind. The TARDIS dematerialises.
Amy and the Doctor return to the Musée d'Orsay, where Amy is optimistic that van Gogh will have lived a long life and created many more paintings: in fact, nothing has changed. The Doctor explains to her his theory that good things can't remove the bad things from life but, equally, the bad things can't spoil the good things. He adds that he believes they certainly added to the good things in Vincent's life. They step over to the painting of the sunflowers which now carries a dedication 'to Amy'.