Though they were finally happy as a couple, Wade (Wilson Bethel) got drunk and cheated on Zoe (Rachel Bilson). Though he tried to hide it for days, the truth came out when his guilt came to be too much ... and because he got caught in his lies. Wade's infidelity was the one thing Zoe couldn't forgive, and she broke up with him.
Why this worked:
When Wade's infidelity was revealed, the fans went crazy, calling the writers of the show lazy and saying that Wade cheating on Zoe wasn't believable since he was so in love with her. I, however, thought that -- while totally heartbreaking -- Wade's infidelity was truthful to who he was as a character. Though he had been evolving as a person throughout the series (he started off as a lazy drunk jerk), he constantly self-sabotages, and he believed himself to be undeserving of Zoe and her love. He may have been trying to be a better person, but the fact that he made a mistake was realistic and totally in the realm of who he is. The writers didn't sacrifice his character to move the plot along. This kind of thing happens in real life, and was portrayed in a realistic way on a show known and loved for its campiness.
-- Sydney Bucksbaum, Zap2it