Callie is trying to avoid Arizona after a crappy date, and so chooses to spend a day in the ER. She jinxes herself by noting that it's totally quiet, and so is rewarded with a number of about-to-be college graduates who were in a horrific car accident. Callie is also being stalked by Arizona, who wants to know why their date went so weird the night before. Callie won't talk to her girlfriend until Arizona finally confronts her at the end of the day because she is so hurt, and Callie spills that she got stressed out going to an expensive restaurant since she has no money anymore. Arizona of course understands, and they decide that they can spend date nights in bed with pizza instead. George is there all day to help out Hunt, but has a very 007 day as six of his patients die despite his rather awesome levelheadedness and trauma skills. He's totally defeated about what happened but Hunt tells him sincerely that he did a great job, and trauma is a team sport. He assures George that he was a crucial part of the team. The lesson that everyone seems to learn from all of the dying (and the single living) patients is that you shouldn't wait to live your life and instead just go for it. While Hunt and Cristina don't go for it, per se, they are at least talking in more than three-word sentences and clearly yearning for each other. Owen tells Cristina that he and his doctor pinpointed the ceiling fan as the trigger that set off the choking incident, so at the end of the night at home she beats it out of the ceiling.
All of this is going on as the hours tick down to Meredith and Derek's wedding. Derek's wedding present to his bride is her first solo surgery, which Richard oversees. He unfortunately hangs too closely over her shoulder and can't be as removed as he was with everyone else, but ultimately she does a fine job. After it's all over, he tells her that her mother would have been proud. Derek wasn't there to witness any of the surgery, however, because he's trying to help Izzie. Denny shows back up again and so Izzie does something shocking and immediately tells her doctors so that they can figure out what's wrong. When nothing shows up on the scan Derek tries out a never-been-done-before procedure (because he is just that good) where they monitor her brain function when she has a hallucination so that he can figure out where the problem is. It works, but it turns out the tumor is so tiny and so deep that he can't operate and he wishes there was something nice he could do for her to make up for the fact that this seems to mean certain death. Izzie has been planning all day for that night's wedding ceremony that she admits out loud is perfect for her and not for Mere and Derek. Yeah -- my head is still sore from the beating I took with the Obvious Stick, but it was executed pretty well when all was said and done. Meredith, Bailey, and Alex in his tux surprise Izzie with the wedding dress and perfect ceremony that she planned from top to bottom. She's thrilled and they have a beautiful ceremony, but when Alex brings her back to the hospital she seems to be in pretty bad shape and her hair is starting to fall out. They shave her head, and then Izzie fully embraces her marriage by telling Denny to go away so she can be alone with her husband.
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George has had his turn, as has Alex, so this week the voiceover duties go to Izzie. Although it's not voiceover, exactly, since she's actually saying these things to someone as she lies in bed, extremely pasty and extra sick-looking and with a pink patterned head scarf, she does set the theme of this week's episode. And who could she possibly be speaking to? Well that's just a surprise for now, unless of course you have ever watched TV before and can guess these "twists" and/or saw any promotional pictures or anything about this landmark 100th episode. "You never know the biggest day of your life is going to be the biggest. The days you think are going to be big ones, they're never as big as you make them out to be in your head.
In a slow-mo close-up we see Bailey's hand fluffing a wedding gown, and another of the woman fixing the strap. Izzie continues, wheezing a bit, "It's the regular days, the ones that start out normal -- those are the days that end up being the biggest. And today was the wedding. It was beautiful, perfect." After some shots of the beautifully decorated church and the guests standing up to see the bride (even though we don't get to see her) we cut to Meredith and Derek standing in the not-yet-decorated church by themselves. Meredith says it's just a normal day; they are going to work and then afterwards they just happen to be getting married in a, "churchy church..." her voice is now annoyed and Derek jumps in to remind her that this has nothing to do with them. "We're just the bride and groom." But Meredith then lightens up and smiles as she says, sounding genuinely pleased, "We're getting married tonight," which he repeats. 100 episodes in, Meredith seems to really have grown into a happy, optimistic person.
Callie is sleeping on a couch in the hospital when she's woken up by an incredibly peeved Cristina, who is upset to find her there since she herself slept in the on-call room instead of at home in her own bed. Her mood was not great to begin with given that she has to work a full day and then, "be happy Maid of Honor and get Meredith down the aisle." So, I guess while viewers can see the changes in Mere, those around her haven't quite gotten how real it is. Apparently Callie asked Cristina to stay away because she thought it was going to be The Night with Arizona, but she tells Cristina that they went to dinner but she then wasn't in the mood, and also she had to be in early to run the ER. Cristina asks, laboring to sound casual, if Hunt isn't in but Callie says that he is and then runs off. Mere then walks in and Cristina puts on her best cheerleader face and rah-rahs, "Big day! Biggest day of your life!" Mercifully, Mere tells her to stop because she's being creepy. Cristina is relieved, but then immediately suspicious that this is just the calm before the storm and asks if she is going to need to drug Mere, or "shave off [her] eyebrows to numb [her] into submission?" Meredith assures her best friend that she is fine, and that she's excited about the marriage, not the wedding. Today is actually the biggest day of Izzie's (possibly short) life. She reminds Cristina that Izzie is the one who has gone bridezilla and Cristina repeats, "Bridezillllaaaaaaaaa," in a hilarious horror-movie voice. It's a total throwaway moment, but it's awesome.