Skillet frontman John Cooper told StereoTruth: "This is definitely an angry song, but it's also tongue in cheek. So many times this is something you say during a break up, but it could also apply to an authority figure or a parent who treats you bad. Even when people weigh us down, we can turn to Christ and find ourselves empowered by putting our hope in Him instead of letting someone who's giving you a hard time wear you down."
In a 2017 interview with the Jesus Calling podcast, Cooper explained how the song saved a man's life: "A guy came to me a few weeks ago and said that his wife cheated on him, and ran off with their kid. He went into depression and wanted to kill himself. He tried to kill himself and he was committed to a psych ward. He ends up hearing our song 'It's Not Me, It's You' and that song made him realize that he was not crazy, that it really was his wife. He went into rehab, he got off of drugs, and here he is five years later - he has sole custody of his kids. He's clean and he was crying telling me the story. I just thought, I cannot believe that song did that. There's a lot of broken people out there, and they need to hear these messages, and they're not going to come to church to hear them. So, we need to go to them. That's what I'm most excited about."
"A lot of people say it's not very Christian," Cooper told The Denver Post of the song. "But it's about self-improvement. It's about someone, something or even yourself bringing you down and then all of a sudden, you realize that it's not you. You are OK. It could be a relationship, a friend. It's something a lot of Christians don't like talking about, but we need to."