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Why it was a game-changer: Owen's return really kicked off the start of his relationship with Cristina, while Callie began a new journey of self-discovery that eventually leads her to Arizona. "A Change Is Gonna Come" — Season 4, Episode 1 What happened: After her failed wedding to Burke (Isaiah Washington), Cristina and Meredith return from the honeymoon to find that Burke has permanently left the hospital.
Meredith also gets a shock when she finds out that her half-sister Lexie Grey is now an intern at Seattle Grace alongside George, who is repeating his intern year after failing his exams.
Unfortunately, Percy uses Izzie (Katherine Heigl) to get ahead, leading her to make an irreparable mistake that costs Izzie her job.
In the end, she leaves Seattle Grace and Alex, thinking he had a hand in her firing.
After Hahn (Brooke Smith) and Callie sleep together, Hahn has the "I see leaves" realization that she is "so, so, so gay," which ultimately leads to the end of their relationship as Callie was still discovering who she is.
Meredith and Cristina (Sandra Oh) are enemies, and Owen (Kevin Mc Kidd) and Callie are unhappily married.
Meanwhile, Addison and Derek (Patrick Dempsey) are still together, while Lexie (Chyler Leigh) has become a drug addict.
Not only that, but it lead to Callie and Arizona's wedding, which — while not the first lesbian nuptials on broadcast television — was certainly a momentous occasion. "The Other Side of This Life Parts 1 and 2" — Season 3, Episode 22 and 23 What happened: The two-hour episode serves as a backdoor pilot for , which sees Addison (Kate Walsh) venture to Los Angeles to reunite with old friends Naomi (played by Merrin Dungey, later replaced by Audra Mc Donald) and Sam (Taye Diggs) in hopes of enlisting their help to get pregnant.
It also marksthe episode where Thatcher Grey's (Jeff Perry) wife Susan (Mare Winningham) dies essentially from hiccups.