When Dean is brought out of hell in Lazarus Rising, Bobby takes the boys to his psychic friend so they can try to find out who (or what) broke him out. Pamela Barnes sizes up the boys and immediately likes them! She flirts with both Dean and "Grumpy." However, during the seance she holds to discover who brought Dean back, she ignores a warning from Castiel (before we meet him) and demands to see the one who did it. He shows himself to her, which burns her eyes right out of their sockets!
A now-blind (but remarkable resilient) Pamela returns in Heaven and Hell to help Anna remember who her father is...and, thereby, who she really is. She leaves when she finds out that Anna's really an angel, saying she's had just about enough of angels!
Finally, Pamela helps Sam and Dean become ghosts through a spell in Death Takes a Holiday so that they can figure out who has kidnapped the Grim Reaper. Unfortunately, it is the demons (trying to break another seal), and Pamela gets caught in the crossfire. A demon kills her before Sam gets his bearings (after being out of his body for some time) and take care of that demon. Pamela hears and feels what Sam does to the demon and, just before she dies, she warns him that he may think he's doing the right thing, but he's not.
We see Pamela once more when the Winchesters are in heaven in Dark Side of the Moon.