Following up on Ruby's lead about demons being after Anna Milton, Sam and Dean Winchester are warned that a powerful demon is coming and Alastair appears possessing this man who he describes as a pediatrician. Both Sam's powers and the demon-killing knife have no effect on Alastair and the group is forced to flee him.
As part of their plan to save Anna who is revealed to be a fallen angel, Ruby summons Alastair who appears once more in the man's form. He tortures her until she tells him where to find the others and in a fight that follows, Alastair fights against Castiel while his followers face Uriel. Castiel proves no match for Alastair, but when Anna regains her grace, the man is vaporized by the flash of white light. While Alastair is initially believed killed as well, it is later revealed that he did survive and the man's wife is still looking for him.