1. To place or rest someone, something, or oneself in a leaning position against someone or something else. I set the ladder up against the wall so I could climb up and peer over. He went over and set himself up against the door to make it clear that he wasn't leaving. I had to set the wounded soldier up against the tree so I could press on ahead to find help.

2. To arrange for someone, something, or oneself to face a particular competitor, trial, or test. I can't believe they set me up against the valedictorian for the first match of the competition. Obviously, she's going to win! The game sets you up against harder and harder challenges the further you progress. She always sets herself up against these impossible goals.