Isaac is a Hunter who lives and works near Lincoln, Nebraska, with his wife Tamara. They have been hunting for eight years, after something supernatural killed their daughter. At some point during those eight years, they met and befriended Bobby Singer. Issac is seen carrying a pump action shotgun and a flask of holy water. He and his wife also have Palo Santo, or "holy wood", and a house full of odds and ends that as of yet are unidentified.
Upon meeting the Winchesters, Issac is reluctant to work with them, blaming them for opening the Devil's Gate and bringing about the end of the world. He is more quick to anger than his wife. While investigating a bar looking for demons, he and Tamara are attacked by the Seven Deadly Sins. Issac is killed by the demon Gluttony, who forces him to down a bottle of Drano. A demon then possesses his corpse to try and trick Tamara, but she stabs him and drives out the demon with a stake of Palo Santo. In the morning, he is given a Hunter's pyre by Tamara.