He lives in a house in the surrounds of City 17, with a man-made giant barrier to protect him from headcrab zombies. He is forced to move when the Dark Reactor explodes, and, as a result, he travels through City 17 searching for means to escape, and takes part in the Uprising, fighting with fellow comrades against the Combine. He was on the other side of the crashed Razor Train, transporting Alyx and Gordon. He hears them but he cannot see or contact them.
At the end of DW1, it is he who gets the Muscle Car and he is knocked out with the vehicle by the resulting blast of the Citadel; however, in DW2, he is saved by Dog who put him out of the rubble.
Frank Harrison seems to suffer severe hallucinations and/or witness paranormal activities, as he frequently sees a bald man in a black suit, moving skeletons, and hears disturbing sounds and screams. The reason for this is unknown for now.