If you thought Dean felt guilty before, you ain't see nothing yet. The end of the most recent episode of Supernatural was a pretty crazy turning point for the eldest Winchester brother. He deliberately chose to kill a monster that Sam had chosen to let go free because he believed she wasn't a threat. And not only did he kill her (which resulted in her young son promising vengeance one day), but he also kept it a secret from Sam. Dean Winchester is doing some pretty shady things right now.
The October 14 episode of Supernatural is a fitting continuation of this episode and revolves around the theme of guilty. The Egyptian god Osiris is committing a string of murders after putting people on trial and judging their guilt. When Dean wanders into down, Osiris focuses on him. And it's no wonder, he's got plenty to feel guilty about lately - justifiable or not. Osiris puts Dean on trial for his life and Sam steps in to defend his brother. But the Winchesters are shocked when Osiris calls a surprise witness (the sneakiest courtroom trick!): Jo's ghost. Cue the flashbacks.