Anna Milton is a fallen angel who was reborn on Earth. She gained the ability to hear the conversations of angels after Dean's resurrection, and because of the voices, she was involuntarily committed to a mental institution with the diagnosis of schizophrenia. Demons have a great interest in her because of this, so Ruby alerts Sam and Dean Winchester, who find and rescue her. However, Castiel and Uriel appear and explain that they have to kill her. The brothers try unsuccessfully to hold them off, but Anna creates a powerful magic spell that sends the angels "far away". Anna claims to have no knowledge of how she knew how to do it. Under hypnosis administered by Pamela Barnes, Anna remembers that she is a fallen angel, having become human because her existence as an angel was dismal due to a lack of emotions and free will. She implies that when she was an angel, she was somewhat the "boss" of Castiel and Uriel.

After falling, she was born to human parents, with her angelic memories suppressed. Anna attempts, with the Winchesters and Ruby, to recover her Grace so that she will be safe from both sides. Unfortunately, her Grace had already been taken by Uriel. Later, she forgives Dean for his actions in Hell, and then they share an intimate night in the Impala. In the morning, Dean reveals to the angels their location, and Ruby does the same for the demons, as they hope to pit the two groups against each other. In the confusion of the fight between the angels and the demons, Anna is able to grab back her Grace from Uriel. It flows into her body, emitting a bright light, and she vanishes from the room. She makes a return in "On the Head of a Pin" with her human form, having "called in favors" to have her human body restored in order to use it as a host. She tries to convince Castiel that forcing Dean to torture Alastair is wrong, but he blows her off as he states it is "God's will". She shows up again after he calls to her for advice as he is having doubts for the first time, but then she vanishes, telling Castiel that he has to learn to think for himself. She shows up one more time to save him from Uriel, after learning of his betrayal, killing him by stabbing him through the neck. She informs the Winchesters that Castiel was recalled to heaven for discipline. Later when Castiel frees Sam from the Demon Panic Room, she confronts him on his actions. Castiel then has two angels take her away.