And by the title, I mean that once you make a decision, or a mistake that changes the storyline, you don't rewind and change your mind. Dying and respawning is okay though.
I'm doing this because I feel that it's the only way to enjoy the game. I don't want to have a perfect playthrough - I'm a human being, I make mistakes, and I want the story of the walking dead to be just as tragic as it would be in real life - if I make a decision or say something I regret, I deal with the consequences.
Two things I regret the most about my playthrough is shooting Jolene in the forest, and siding against Lily in the meat locker.