An episode entitled “Didn’t We Almost Have It All” leaves a foreboding feeling in the air from the start. What will become of the race for Chief, the Chief's wife, the wedding, the intern in love with his patient and unwilling to admit it, the other intern in love with her married best friend, and the growing rift between Meredith and Derek? And there's the matter of the fourth rock climber with an ax lodged in his skull. We learn that this happened not because of an accident, as the trio of previously-admitted climbers originally tell the cops, but because he was badly hurt and suffering and one of them tried to kill him to put him out of his misery. Derek realized it was intentional during brain surgery on the man, and he confronted them until they caved.

With police and lawyers arriving on the scene, the man who wielded the axe defended his motives, saying he’d do it again if he had to. Derek is left wondering if he should be put out of his own misery, relationship-wise. After meetings with Addison, Mark and Preston in which he turns each down, Richard gives Derek the news that he's being recommended for the Chief of Surgery position. But Shepherd turns it down, telling Richard that there's a better man for the job - Richard. If he really wishes he could do it all over again, Derek says, then he should. The Chief's future remains up in the air, then, as he reconciles (at least somewhat) with Adele. He remains by her side throughout her operation, and afterwards, after they learn Adele miscarried the baby, she reveals it was Richard's child all along. Adele says she thought he'd go running for the hills, but she misjudged him. After all that's happened, there's hope for these two yet.

Jeff Pope, Rebecca's husband, comes to reclaim his wife. Like Rebecca said, her husband is a nice guy - one who admits privately to Alex that he didn’t pay enough attention to her. He loves her and is ready to bring her and the baby. Alex is disappointed, but when Rebecca tells him he’s the only one who saw the real her and begs him to give her a reason to stay, he can't. It seemed as if he was letting Rebecca go because he didn’t want to make her stay, only to disappoint her. Or because he can't face the fact that he's got real feelings for someone. Later, Addison (of all people) tells Alex he sucks, and that he can't leave life-changing opportunities on the table. He races back to Seattle Grace... to find Rebecca's hospital room tragically empty.

Elsewhere, Callie wants to have a baby, and after some deliberation, George is apparently into the idea. They even tried to make one in the break room, she reveals. Oh, and she was named Chief Resident, stunning Dr. Bailey and pretty much everyone else except her newly-confident self. But it's her and George that Izzie can't bear. Right before the Burke-Cristina wedding, Izzie confesses that she’s still in love with him after saying she’d do everything to support his marriage with Callie if that's what he really wants. They shared deep eye-contact after her profession of love, but nothing more. If he shares her feelings, he's not saying. George has other problems than his turbulent love life, however. He learns he didn’t pass his intern exam, although he doesn't tell anyone. Bailey knows, of course, and after asking if she failed him, says he can either walk away from being a surgical resident altogether, or repeat his intern year. George says it's him that failed her, and walks.

As he's cleaning out his locker, the newest crop of interns arrives, taking a self-guided tour of the hospital. A beautiful girl stays behind to ask him for advice, introducing herself as Lexie Grey. Lexie Grey can only be Meredith's half-sister, and is also recognizable as the girl Derek flirted with in the bar the night before. Amazing. Earlier, Derek admits to Meredith that he flirted with the girl in the bar and it was the highlight of his week. Later, though, he tells Meredith that he loves her and will never leave her, but she keeps leaving him. She comes and goes whenever it’s convenient. He tells her that if she’s not in it for the long haul, she needs to leave him for good. Meredith gets teary, remains non-committal and says she needs to go to help Cristina.

Just before the wedding, best man Derek tells Preston he doesn’t think he and Meredith are going to make it. He also lies and says he got turned down for the Chief of Surgery job, which we don't know to be a lie at the time. Cristina and Preston are about to get married. The moment has arrived. But after Cristina freaks out because her vows - written on her hand - washed off when she scrubbed in earlier that day, Burke goes out to find her and in a moment of clarity, decides he knows she didn’t want to marry him. He says she would, because she loves him, but doesn't want to. She tried to argue with him, but both knew what he was saying was true. In the closing moments, she goes back to their apartment to find Burke is gone. Meredith asks how she knows for sure, and Cristina points out the absence of his trumpet, jazz collection, lucky scrub cap and a picture of his grandmother. They're all missing. Cristina tells Meredith she’s free, then bursts into tears. Anxiety consumers her and she begs to get out of the dress. Meredith literally cuts the back off it as she collapses into her arms in emotional anguish.