"What A Difference A Day Makes" is the twenty-second episode of the fifth season of Grey's Anatomy and the 100th produced episode of the series. It is also the 131st produced episode of the Grey's Anatomy franchise. It was broadcast on May 7, 2009.
Meredith and Derek's wedding day arrives, Izzie fears the worst when she begins to experience familiar symptoms and the reoccurance of her visions leads Derek to make a discovery about Izzie's illness and an unexpected suggestion to Meredith. Owen, Callie, George and Lexie deal with a group of college students admitted to the E.R after a crash on their way to their graduation. Callie's monetary issues interfere with her relationship with Arizona while Cristina gets an insight into Owen's trauma.
- "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 are never as big as you make them out to be in your head. 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."
- "You don't recognize the biggest day of your life, not until you're right in the middle of it. The day you commit to something, someone. The day you get your heart broken. The day you meet your solemate. The day you realize there's not enough time because you want to live forever. Those are the biggest days, the perfect days."
- "First In Line " - Matthew Mayfield
- "Another Likely Story" - Au Reviour Simone
- "Turn To Stone" - Ingrid Michaelson
This episodes' title references the song What A Difference A Day Makes, originally sung by Dinah Washington
- Izzie narrates the voiceover for episode.
- A working title for this episode was Beautiful Day